takotsubo cardiomyopathy in acute ischemic stroke

Takotsubo Cardiomyopathy in AcuteIschemic Stroke

Sohei Yoshimura, MD, Kazunori Toyoda, MD, Tomoyuki Ohara, MD, Hikaru Nagasawa, MD,Noriko Ohtani, MD, Takahiro Kuwashiro, MD, Hiroaki Naritomi, MD, and Kazuo Minematsu, MD

Objective: Takotsubo cardiomyopathy, which is characterized by transient left ventricular apical ballooning, is a known com-plication of subarachnoid hemorrhage. The aim of this study was to identify the clinical characteristics of acute ischemic strokepatients who experienced development of takotsubo cardiomyopathy.Methods: Seven patients who were diagnosed as having takotsubo cardiomyopathy based on their electrocardiographic andechocardiographic findings were studied. They were selected from among 569 consecutive patients who were admitted to ourstroke center within 24 hours after onset of acute ischemic stroke. The findings of nine previously published cases were alsoreviewed.Results: All seven patients were women, and six were 75 years or older. The initial National Institutes of Health Stroke Scalescore ranged from 3 to 28. The culprit infarcts included or were close to the insular cortex in six patients and were locatedextensively in the vertebrobasilar arterial territory in the other patient. Abnormal findings on electrocardiographic monitoringappeared within 10 hours after stroke onset in five patients and at 6 and 12 days, respectively, in the other two patients. Thecardiomyopathy was symptomatic in only two patients. Plasma brain natriuretic peptide levels exceeded the upper normal limitby 10-fold in all patients. The previously published cases were mostly women and had mainly vertebrobasilar stroke.Interpretation: Takotsubo cardiomyopathy is not a rare complication of acute ischemic stroke. It most often occurred soonafter stroke onset and was commonly asymptomatic. Female sex and insular damage were predominant features of the strokepatients who experienced development of takotsubo cardiomyopathy.

Ann Neurol 2008;64:547–554

Takotsubo cardiomyopathy (apical ballooning syn-drome, ampulla cardiomyopathy, stress cardiomyopa-thy) is characterized by transient left ventricular apicalballooning that resembles a Japanese octopus catcherpot (takotsubo) with a short narrow neck and roundbottom.1,2 The typical electrocardiogram (ECG) ab-normalities are ST elevation in the acute phase fol-lowed by giant negative T waves, most frequently inleads V3 and V4.3,4 The abnormality of left ventricularwall motion sometimes mimics acute coronary syn-drome, but it extends beyond a single epicardial vascu-lar distribution and improves within weeks in mostcases. Profound psychological stresses, including earth-quakes, gambling loss, and estrangement from family,trigger this unique syndrome.5,6 Although the precisecause of this syndrome is still unknown, possible mech-anisms include catecholamine-induced myocardialstunning, ischemia-mediated stunning caused by mul-tivessel epicardial or microvascular spasm, and myocar-ditis.3,4 In particular, frequent occurrence of precedingpsychological events suggests a key role of cat-

echolamines in triggering the syndrome. Wall motionabnormalities have been observed in conditions associ-ated with catecholamine surge, including a pheochro-mocytoma.7 In a recent classification of cardiomyopa-thies advocated by the American Heart Association,takotsubo cardiomyopathy was ranked as a primary ac-quired cardiomyopathy.8

Takotsubo cardiomyopathy is a well-known compli-cation of subarachnoid hemorrhage (SAH); massivecatecholamine release caused by the hemorrhage maytrigger the cardiomyopathy.9,10 On the other hand, theoccurrence of this complication in patients with acuteischemic stroke has not been systematically examined.

The goal of this study was to identify the clinicalcharacteristics of acute ischemic stroke patients who ex-perienced development of takotsubo cardiomyopathy.

Patients and MethodsBetween February 2005 and October 2006, 569 patientswere admitted to our stroke center within 24 hours after on-set of acute ischemic stroke. All patients underwent ECG

From the Cerebrovascular Division, Department of Medicine, Na-tional Cardiovascular Center, Suita, Osaka, Japan.

Received Apr 9, 2008, and in revised form May 29. Accepted forpublication Jun 13, 2008.

Published online Aug 6, 2008, in Wiley InterScience(www.interscience.wiley.com). DOI: 10.1002/ana.21459

Potential conflict of interest: Nothing to report.

Address correspondence to Dr Toyoda, Cerebrovascular Division,Department of Medicine, National Cardiovascular Center, 5-7-1Fujishiro-dai, Suita, Osaka 565-8565, Japan.E-mail: [email protected]

© 2008 American Neurological Association 547Published by Wiley-Liss, Inc., through Wiley Subscription Services

monitoring during the initial several days they were hospi-talized in our stroke care unit (for at least 24 hours); longerECG monitoring was performed if necessary. The criteriaused to identify patients experiencing development of takot-subo cardiomyopathy during the initial days of hospitaliza-tion included: (1) appearance of abnormal ECG findings, in-cluding ST-segment elevation and negative giant T wavesduring the initial days of hospitalization that were absent onadmission (Fig 1A); and (2) “balloon-like asynergy,” whichinvolves circumferential hypokinesis, akinesis, or dyskinesisof mid and apical segments of left ventricle with normal orhypercontraction of the basal segment on echocardiogram,whereas ECG showed the abnormal findings (see Fig 1B). Pa-tients who satisfied both criteria were prospectively enrolled.

The following underlying risk factors were examined: sex,age, history of cardiopulmonary disease and stroke, hyperten-sion (blood pressure � 140/90mm Hg before stroke or his-tory of antihypertensive medication), diabetes mellitus (fast-ing blood glucose � 126mg/dl, positive 75gm oral glucosetolerance test, or history of antidiabetic medication), hyper-cholesterolemia (serum total cholesterol � 220mg/dl or his-tory of antihypercholesterolemic medication), current or pre-vious smoking habit, and alcohol consumption of 2 or moredrinks per day.

Ischemic stroke was defined as focal neurological symp-toms for which diffusion-weighted magnetic resonance imag-

ing (MRI), or computed tomography if MRI was contraindi-cated, demonstrated corresponding infarcts. Cephalocervicalarterial lesions were assessed using magnetic resonance an-giography, unless contraindicated, and ultrasound for all pa-tients. Based on neurological, radiological, and cardiologicalfindings, the stroke subtype was determined by trained vas-cular neurologists according to the TOAST (Trial of Org10172 in Acute Stroke Treatment) subtype classification sys-tem.11 Neurological deficits were evaluated using the Na-tional Institutes of Health Stroke Scale score on admissionand at discharge around 3 weeks after stroke onset. Thegrade of disability was assessed using the modified RankinScale score at discharge.

In addition to the ECG and echocardiogram examina-tions, creatine kinase and its myocardial band (MB) subtype,troponin-T, and brain natriuretic peptide (BNP) levels weremeasured in the blood as indicators of cardiac changes. Car-diac MRI and coronary angiography were performed ifneeded.

In addition, all available published case reports on cardiacdysfunction occurring in acute ischemic stroke patients thatwas attributable to takotsubo cardiomyopathy were identifiedin the PubMed database using the following search terms:“takotsubo cardiomyopathy,” “stress-induced cardiomyopa-thy,” “apical ballooning,” “broken heart syndrome,” “myo-cardial stunning,” or “cardiac dysfunction”; and “ischemic

Fig 1. Typical electrocardiogram and echocardiogram in takotsubo cardiomyopathy. (left panels) Electrocardiographic (ECG) changesin Patient 2 on admission (A), at 4 days (B), and at 3 weeks (C). (right panels) Four-chamber view of ECG of Patient 3 show-ing balloon-like asynergy of the apical region (white arrow) and hypercontraction of the basal segment (black arrows).

548 Annals of Neurology Vol 64 No 5 November 2008

stroke” or “cerebral infarction”. The Japanese literature wasalso searched using the Web of Japana Centra Revuo Medi-cina with the following terms: “takotsubo,” and “brain in-farction” or “artery occlusion”.

ResultsAnalyses of the Seven Patients Admitted to OurStroke CenterOf the 569 patients studied, 7 (1.2%) were diagnosedas having takotsubo cardiomyopathy. All patients were

women and 75 years or older, except for a 47-year-oldwoman (Patient 7; Table 1). Six patients had historiesof cardiopulmonary disease. One (Patient 3) had a pre-vious history of a mild ischemic stroke in the left pa-rietal lobe. Five patients had one or more vascular riskfactors.

Four patients (Patients 1–4) experienced develop-ment of an infarct in a unilateral hemisphere includingthe insular cortex caused by cardiogenic or aortogenic

Fig 2. Distribution of brain infarcts for the seven patients.

Table 1. Underlying Characteristics and Stroke Features for Seven Patients

PatientNo.

Sex Age,yr

History ofCardiopulmonary

Disease

Historyof

Stroke

VascularRisk

Factors

StrokeSubtype

ArterialLesion

MajorNeurological

Signs

AdmissionNIHSS

NIHSS atDischarge

mRS atDischarge

1 F 78 Pulmonarytuberculosis

None HT,smoking,drinking

Other(aotogenicembolism)

None Hemiparesis,aphasia

9 3 2

2 F 90 AF, AS, CHF None Smoking Cardiogenicembolism

R ICAocclusion

Hemiparesis,USN,anosognosia

15 14 4

3 F 78 AF Ischemicstroke

None Cardiogenicembolism

None Hemiparesis,aphasia

19 17 5

4 F 75 AF, MSR, CHF None HT, HC Cardiogenicembolism

None Hemiparesis 3 0 0

5 F 82 Pulmonarytuberculosis

None HT, HC Other None Hemiparesis 8 8 4

6 F 80 None None HT, DM Other None Hemiparesis 6 19 5

7 F 47 PFO None None Other BA occlusion(dissection)

Tetraparesislocked-in

28 25 5

NIHSS � National Institutes of Health Stroke Scale; mRS � modified Rankin Scale; HT � hypertension; AF � atrial fibrillation;AS � aortic stenosis; CHF � congestive heart failure; ICA � internal carotid artery; USN � unilateral spatial neglect; MSR � mitralstenosis with regurgitation; HC � hypercholesterolemia; DM � diabetes mellitus; PFO � patent foramen ovale; BA � basilar artery.

Yoshimura et al: Cardiomyopathy in Stroke 549

embolism; one of these patients (Patient 2) had an em-bolic occlusion of the right internal carotid artery (seeTable 1; Fig 2). Two patients (Patients 5 and 6) had abasal ganglia infarct that gradually expanded close tothe insular area and caused neurological deterioration;their diagnosis may have been branch atheromatousdisease. The remaining young patient (Patient 7) expe-rienced development of bilateral cerebellar and pontineinfarcts with basilar artery occlusion caused by dissec-tion. All seven patients had motor paresis, three (Pa-tients 1–3) had cortical signs, and one (Patient 7) hada locked-in syndrome. During the first several days, allpatients received intravenous anticoagulation using un-fractionated heparin (Patients 1–4) or argatroban (Pa-tients 5–7), primarily to prevent embolic events fromthe hypokinetic cardiac wall caused by the cardiomy-opathy. During their hospitalization, no patients hadstroke recurrence. Five patients needed a wheelchair fordaily living at the time of discharge, corresponding to amodified Rankin Scale score of 4 or 5.

The cardiomyopathy was symptomatic in only twopatients (Patients 2 and 4) (Table 2). ECG changesappeared within 10 hours after stroke onset in five pa-tients (Patients 1–5), and at 6 and 12 days, respec-tively, in the other two patients (Fig 3). In all sevenpatients, echocardiography showed localized left ven-tricular hypokinesis around the apical area. In six pa-tients who received follow-up echocardiography (exceptfor Patient 3), the hypokinesis improved within amonth. For two of three patients who underwent car-diac MRI (Patients 4 and 5), unusual hypokinesis orakinesis was identified on cine image; the remainingpatient (Patient 1) had normal MRI findings 3 weeksafter stroke onset, when her ECG and echocardiogra-

phy were also normal. For two patients who underwentcoronary angiography (Patients 1 and 5), the coronaryarteries were not stenotic. Of the cardiac enzymes, onlythe BNP level showed a marked increase (�10-fold in-crease of the upper normal limit). For one patient (Pa-tient 5), virus titers were measured twice on days 12and 33; no virus titers including echoviruses and cox-sackie viruses were elevated. Except for two patientswho had pre-existing valvular disease and heart failure(Patients 2 and 4), none had heart failure at discharge.

Literature ReviewTo the best of our knowledge, nine patients have beenreported as developing an unusual cardiomyopathyduring acute ischemic stroke that was attributable totakotsubo cardiomyopathy: two were English case re-ports (Cases 8 and 9),12,13 three were Japanese case re-ports (Cases 10–12),14–16 and four were Japanese con-ference abstracts (Cases 13–16) (Table 3).17–19 Ofthese nine patients, seven were women, and the pa-tients’ ages ranged from 60 to 85 years. The location ofbrain infarcts or arterial lesions was described in sevenpatients; four had a vertebrobasilar stroke (Patients 11and 14–16), including a patient with a definite basilarartery occlusion that recanalized after intraarterialthrombolysis (Patient 11). Of the four patients whosecardiopulmonary symptoms could be assessed, one wasasymptomatic (Patient 9). ECG changes appearedwithin 6 days after stroke onset in all patients. In twopatients, the initial ECG already documented abnor-malities (Patients 11 and 12); thus, the cardiomyopa-thy may have developed before the stroke.

Table 2. Characteristics of Cardiomyopathy for Seven Patients

PatientNo.

CardiopulmonarySymptom

Electrocardiography Echocardiography

Appearance ofChangea

STElevation

AbnormalQ

NegativeGiant T

% FS Apical WallMotion

1 None 5 hours Present Present Present 40 Severehypokinesis

2 Chest pain 9.5 hours Absent Absent Present 12 Akinesis3 None 8 hours Present Absent Present 34 Severe

hypokinesis4 Respiratory

discomfort2.5 hours Present Absent Present 30 Akinesis

5 None 5 hours Present Present Present 27 Akinesis6 None 6 days Present Present Present 45 Akinesis7 Unclear (because

of locked-insyndrome)

12 days Absent Absent Present 21 Severehypokinesis

aTime interval between stroke onset and electrocardiographic change.NYHA � New York Heart Association; FS � fractional shortening; CK � creatine kinase (reference value: 45-163U/L), CK-MB �creatine kinase myocardial band (�0.23U/L): Troponin-T (�0.25ng/ml); BNP � brain natriuretic peptide (�20.0pg/ml).


DiscussionThis is the first study to present a series of acute isch-emic stroke patients who experienced development of ta-kotsubo cardiomyopathy. The major findings included:(1) 1.2% of the consecutive inpatients with acute isch-emic stroke experienced development of takotsubo car-diomyopathy; (2) all patients with takotsubo cardiomy-opathy in our center and most of the previously reportedpatients were women, and they were generally elderly;(3) the preceding stroke was generally severe, and theculprit infarcts mainly included or were close to theinsular cortex in most of our cases, whereas the ver-tebrobasilar arterial territory was affected in one ofour cases and in some of the previously reported cas-es; (4) ECG changes often appeared within 10 hoursafter stroke onset, although most of the ECG changeswere not associated with cardiac symptoms; and (5)

marked plasma BNP level increase was indicative ofcardiomyopathy.

Although the precise incidence of takotsubo cardio-myopathy is unknown, it has been estimated to occurin 1.5 to 2.2% of patients with acute coronary syn-drome.3 Dysfunction of left ventricular regional wallmotion occurs in approximately 18% of SAH pa-tients,20 and takotsubo cardiomyopathy was identifiedon ECG and imaging studies in 8 of 661 (1.2%) SAHpatients.10 At least one patient with intracerebral hem-orrhage was reported to have experienced developmentof takotsubo cardiomyopathy.21 This incidence of ta-kotsubo cardiomyopathy in ischemic stroke patients(1.2%) suggests that the cardiomyopathy is as impor-tant a complication of ischemic stroke as of SAH. Themain reasons for underestimating takotsubo cardiomy-opathy in acute ischemic stroke appear to be that thissyndrome is reversible and sometimes asymptomatic,and some stroke patients have communication prob-lems and difficulty in complaining about cardiac symp-toms. A relatively high frequency of reports dealingwith takotsubo cardiomyopathy from Japan may bebecause of a racial difference in the incidence of thisdisease. A high female predominance of takotsubocardiomyopathy has been reported in most studiesand reviews, and the patients were generally elder-ly.3,4,10,22 The hormonal changes that occur in post-menopausal women may be related to the causativemechanism.

Electrical stimulation of the rat insular cortex trig-gers tachycardia, bradycardia, heart block leading to es-cape rhythms, and asystole.23,24 Intraoperative insularstimulation in epileptic patients often produces brady-

Fig 3. T-wave amplitude changes in V4 of Patients 2 (cir-cles), 4 (squares), 5 (�), and 6 (triangles). X � Pt. No. 5.

Table 2. Continued

Peak Titer of Myocardial Markers CoronaryAngiography

NYHA

CK(U/L)

CK-MB(U/L)

Troponin-T(ng/ml)

BNP(pg/ml)

OnAdmission

AtDischarge

183 Undone 0.01 1,182.3 No stenosis I I

118 Undone 0.01 651.6 Undone IV III133 26 0.3 undone Undone I I

53 11 0.05 374.7 Undone IV IV

308 20 Undone 605.7 No stenosis I I67 5 Undone 265.5 Undone I I120 14 0.1 1065.7 Undone I I


cardia and depressor responses.25 Patients with an in-sular infarct (particularly right sided) have been re-ported to show decreased heart rate variability, and anincreased incidence of complex arrhythmias and sud-den death.26 Thus, the insular cortex appears to play amajor role in autonomic control of cardiac activity.The predilection for infarct location at or close to theinsular cortex in our patients suggests that insular isch-emia is strongly associated with takotsubo cardiomyop-athy in acute stroke. The medulla is also known to bethe center of autonomic modulation of cardiovascularactivity. The nucleus ambiguus, the nucleus tractussolitarius, the dorsal motor nucleus of the vagus, andthe rostral ventrolateral medulla control the cardiovas-cular system through the afferent pathway from barore-ceptors and the efferent pathway to the heart, vessels,and adrenal glands. Thus, extensive brainstem ischemiamay induce autonomic disturbances and cause takot-subo cardiomyopathy.

Because takotsubo cardiomyopathy sometimes causescongestive heart failure, cardioembolism,27 and sud-den death, screening using ECG monitoring appearsto be important, particularly in elderly female patientswith insular or vertebrobasilar infarcts. Ischemic myo-cardial markers in patients with takotsubo cardiomy-opathy, including creatine kinase, its MB subtype,and troponin-T, are generally within normal lim-its.2,28 On the other hand, BNP levels have been re-ported to increase to an average of more than 500pg/

ml.28 BNP is known to be related to left ventricularsystolic and diastolic dysfunction29; thus, suddenchanges in left ventricular function caused by takot-subo cardiomyopathy may accelerate BNP produc-tion. With respect to other noninvasive diagnosticprocedures, 123I-metaiodobenzylguanidine myocardialscintigraphy documents ventricular asynergy causedby cardiac sympathetic hyperactivity.30 On cardiacMRI, takotsubo cardiomyopathy shows left ventricu-lar apical ballooning on cine image and no delay ofgadolinium enhancement.31 Measurement of virus ti-ters appears to be available for differentiating takot-subo cardiomyopathy from viral myocarditis.32 Al-though myocarditis would be one of the mechanismsof takotsubo cardiomyopathy, recent reviews do notsupport this possibility because several studies couldnot demonstrate biopsy evidence or typical cardiacMRI findings that were compatible with myocardi-tis.3,4

The features of the commonly seen “stunning” afterSAH appear to be somewhat different from those of thiscardiomyopathy after ischemic stroke. The largest differ-ence is distribution of regional wall-motion abnormality.After SAH, the basal and mid-ventricular segments arefrequently affected, and there was relative sparing of theapical segments.33,34 SAH-induced cardiomyopathy ismost commonly associated with diffuse T-wave inver-sions and left ventricular dysfunction at hospital arrivalwith gradual improvement. In addition, an increased

Table 3. Literature Review

PatientNo.

First Author(publication year)

Sex Age,yr

Site of Infarct ArterialLesion

NeurologicalSigns

8 Wang (1997)12 F 65 R parietotemporalarea

ND Hemiparesis

9 Sadamatsu(2000)13

M 65 ND ND ND

10 Nakamura(2003)14

F 81 L putamen–corona radiata

ND Hemiparesis

11 Ueno (2006)15 F 61 Vertebrobasilar(multiple)

BAocclusion

Tetraparesis

12 Matsui (2007)16 F 85 L anterior cerebralartery territory

ND Hemiparesis

13 Kato (1998)17 F 75 ND ND ND

14 Kamizuma(2001)18

F 60 R cerebellum ND Ataxia

15 Sugie (2004)19 F 78 ND Possible BAocclusion

Coma

16 Sugie (2004)19 M 74 BA territory Possible BAocclusion

Coma

aTime interval between stroke onset and electrocardiographic (ECG) change.bThe stenoses did not correspond to the regional wall-motion abnormality.NYHA � New York Heart Association; ND � not described; RCA � right coronary artery; LAD � left anterior descending artery;BA � basilar artery.


troponin level is an available marker.34–36 These differ-ences suggest different severity of cardiac damage or dif-ferent mechanism of cardiomyopathy between patientswith SAH and those with ischemic stroke.

This study had several limitations. Because most ofthe consecutive stroke patients underwent ECG moni-toring only for the initial several days, development ofcardiomyopathy during the later phase might havebeen overlooked. Because most of the patients withcardiomyopathy did not undergo coronary angiogra-phy, primarily because of its invasiveness, the effect ofcoronary artery lesions on cardiomyopathy might havebeen underestimated. Among patients who alreadyshowed abnormal findings on the initial ECG right af-ter hospital arrival and who were thus excluded fromthis study, there might have been some patients whoexperienced development of takotsubo cardiomyopathybetween stroke onset and hospital arrival. Finally, datawere lacking for some of the reported cases.

In conclusion, takotsubo cardiomyopathy was not arare complication of acute ischemic stroke and was of-ten asymptomatic. Female sex and insular damage werepredominant features of the patients having takotsubocardiomyopathy. Long-term ECG monitoring, as wellas repeated ultrasound examinations once specific ab-normalities are identified on ECG, can be used topromptly detect and then appropriately manage thisunique complication.

This study was supported by Grants-in-Aid from the Ministry ofHealth, Labour and Welfare, Japan (H20-Junkanki-Ippan-019;Chief Investigator, Kazunori Toyoda).

References1. Dote K, Sato H, Tateishi H, et al. Myocardial stunning due to

simultaneous multivessel coronary spasms: a review of 5 cases[in Japanese]. J Cardiol 1991;21:203–214.

2. Tsuchihashi K, Ueshima K, Uchida T, et al. Transient left ven-tricular apical ballooning without coronary artery stenosis: anovel heart syndrome mimicking acute myocardial infarction.Angina pectoris-myocardial infarction investigations in Japan.J Am Coll Cardiol 2001;38:11–18.

3. Bybee KA, Kara T, Prasad A, et al. Systematic review: transientleft ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med2004;141:858–865.

4. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome(tako-tsubo or stress cardiomyopathy): a mimic of acute myo-cardial infarction. Am Heart J 2008;155:408–417.

5. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and revers-ible cardiomyopathy provoked by stress in women from theUnited States. Circulation 2005;111:472–479.

6. Sato M, Fujita S, Saito A, et al. Increased incidence of transientleft ventricular apical ballooning (so-called ‘Takotsubo’ cardio-myopathy) after the mid-Niigata Prefecture earthquake. Circ J2006;70:947–953.

7. Sanchez-Recalde A, Costero O, Oliver JM, et al. Images in cardio-vascular medicine. Pheochromocytoma-related cardiomyopathy: in-verted Takotsubo contractile pattern. Circulation 2006;113:e738–e739.

Table 3. Continued

CardiopulmonarySymptom

Appearance ofECG Changea

Apical Wall Motionon Echocardiogram

CoronaryAngiography

AdmissionNYHA

NYHA atDischarge

Dyspnea Severalminutes

Severe hypokinesis Untested I (dead)

Asymptomatic 3 days Akinesis Stenosis of RCAand LADb

I I

Chest pain 5 hours Akinesis No stenosis I I

Unclear (becauseof coma)

On admission Hypokinesis Untested ND I

Respiratorydiscomfort

On admission Akinesis No stenosis ND ND

ND 3 days Akinesis No stenosis ND ND

ND 6 hours Hypokinesis ND ND ND


6 days Severe hypokinesis ND ND ND


6 days Severe hypokinesis ND ND ND


8. Maron BJ, Towbin JA, Thiene G, et al. Contemporary defini-tions and classification of the cardiomyopathies: an AmericanHeart Association Scientific Statement from the Council onClinical Cardiology, Heart Failure and TransplantationCommittee; Quality of Care and Outcomes Research andFunctional Genomics and Translational Biology Interdiscipli-nary Working Groups; and Council on Epidemiology and Pre-vention. Circulation 2006;113:1807–1816.

9. Mayer SA, LiMandri G, Sherman D, et al. Electrocardiographicmarkers of abnormal left ventricular wall motion in acute sub-arachnoid hemorrhage. J Neurosurg 1995;83:889–896.

10. Lee VH, Connolly HM, Fulgham JR, et al. Tako-tsubo cardio-myopathy in aneurysmal subarachnoid hemorrhage: an undera-ppreciated ventricular dysfunction. J Neurosurg 2006;105:264–270.

11. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classificationof subtype of acute ischemic stroke: definitions for use in amulticenter clinical trial. TOAST. Trial of Org 10172 in AcuteStroke Treatment. Stroke 1993;24:35–41.

12. Wang TD, Wu CC, Lee YT. Myocardial stunning after cere-bral infarction. Int J Cardiol 1997;58:308–311.

13. Sadamatsu K, Tashiro H, Maehira N, Yamamoto K. Coronarymicrovascular abnormality in the reversible systolic dysfunctionobserved after noncardiac disease. Jpn Circ J 2000;64:789–792.

14. Nakamura A, Asano M, Katagiri K. A case report of ampulla-like shape left ventricular abnormality induced by the stress ofcerebral infarction [in Japanese]. Heart (Japan Heart Founda-tion) 2003;35:509–515.

15. Ueno U, Inoue T, Shibazaki K, et al. A case of takotsubo car-diomyopathy associated with embolic basilare artery occlusion[in Japanese]. Jpn J Stroke 2006;28:297–300.

16. Matsui A, Takada H, Tsubakimoto K. Takotsubo cardiomyop-athy [in Japanese]. Rinsho to Kenkyu 2007;84:1241–1244.

17. Kato R, Saito M, Matsuo K. Abstract of case presentation ontakotsubo cardiomyopathy [in Japanese]. Jpn Circ J 1998;62:708.

18. Kamizuma R, Hata T, Mitsueda R. Abstract of case presenta-tion on takotsubo cardiomyopathy [in Japanese]. RinshoShinkeigaku 2001;41:715.

19. Sugie R, Kohata H, Miki Y. Abstract of case presentation ontakotsubo cardiomyopathy [in Japanese]. Jpn J Stroke 2004;26:192.

20. Kothavale A, Banki NM, Kopelnik A, et al. Predictors of leftventricular regional wall motion abnormalities after subarach-noid hemorrhage. Neurocrit Care 2006;4:199–205.

21. Deininger MH, Radicke D, Buttler J, et al. Tako-tsubocardiomyopathy: reversible heart failure with favorable outcomein patients with intracerebral hemorrhage. Case report. J Neu-rosurg 2006;105:465–467.

22. Gianni M, Dentali F, Grandi AM, et al. Apical ballooning syn-drome or takotsubo cardiomyopathy: a systematic review. EurHeart J 2006;27:1523–1529.

23. Oppenheimer SM, Cechetto DF. Cardiac chronotropic organi-zation of the rat insular cortex. Brain Res 1990;533:66–72.

24. Oppenheimer SM, Wilson JX, Guiraudon C, Cechetto DF. In-sular cortex stimulation produces lethal cardiac arrhythmias: amechanism of sudden death? Brain Res 1991;550:115–121.

25. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardio-vascular effects of human insular cortex stimulation. Neurology1992;42:1727–1732.

26. Tokgozoglu SL, Batur MK, Topuoglu MA, et al. Effects ofstroke localization on cardiac autonomic balance and suddendeath. Stroke 1999;30:1307–1311.

27. Grabowski A, Kilian J, Strank C, et al. Takotsubocardiomyopathy: a rare cause of cardioembolic stroke. Cerebro-vasc Dis 2007;24:146–148.

28. Akashi YJ, Musha H, Nakazawa K, Miyake F. Plasma brainnatriuretic peptide in takotsubo cardiomyopathy. QJM 2004;97:599–607.

29. Omland T, Aakvaag A, Bonarjee VV, et al. Plasma brain natri-uretic peptide as an indicator of left ventricular systolic functionand long-term survival after acute myocardial infarction: com-parison with plasma atrial natriuretic peptide and N-terminalproatrial natriuretic peptide. Circulation 1996;93:1963–1969.

30. Akashi YJ, Nakazawa K, Sakakibara M, et al. 123I-MIBG myo-cardial scintigraphy in patients with “takotsubo” cardiomyopa-thy. J Nucl Med 2004;45:1121–1127.

31. Teraoka K, Kiuchi S, Takada N, et al. Images in cardiovascularmedicine: no delayed enhancement on contrast magnetic reso-nance imaging with takotsubo cardiomyopathy. Circulation2005;111:e261–e262.

32. Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ven-tricular dysfunction with ST-segment elevation: a novel cardiacsyndrome mimicking acute myocardial infarction. Am Heart J2002;143:448–455.

33. Zaroff JG, Babcock WD, Shiboski SC, et al. Temporal changesin left ventricular systolic function in heart donors: results ofserial echocardiography. J Heart Lung Transplant 2003;22:383–388.

34. Banki N, Kopelnik A, Tung P, et al. Prospective analysis ofprevalence, distribution, and rate of recovery of left ventricularsystolic dysfunction in patients with subarachnoid hemorrhage.J Neurosurg 2006;105:15–20.

35. Horowitz MB, Willet D, Keffer J. The use of cardiactroponin-I (cTnI) to determine the incidence of myocardialischemia and injury in patients with aneurysmal and presumedaneurysmal subarachnoid hemorrhage. Acta Neurochir (Wien)1998;140:87–93.

36. Tung P, Kopelnik A, Banki N, et al. Predictors of neurocardio-genic injury after subarachnoid hemorrhage. Stroke 2004;35:548–551.


takotsubo cardiomyopathy in acute ischemic stroke

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