Shinshu Med J, 70⑴：39～46, 2022

Prevalence of Takotsubo Syndrome among Patients Admitted to
an Emergency Department
Akihiro Yashio1）, Hiroshi Imamura2）＊, Katsunori Mochizuki2）, Yuichiro Kashima2）
Hiroshi Takayama2）, Kenichi Nitta2）, Kanako Takeshige2） and Hiroshi Kamijo2）
1） Department of Emergency and Critical Care Medicine, Otsu City Hospital2） Department of Emergency and Critical Care Medicine, Shinshu University Hospital

Aim : Takotsubo syndrome (TTS) is identified in 1-3 ％ of patients with suspected acute coronary syndrome andis a complication of various diseases. This study aimed to clarify the prevalence and clinical characteristics of
TTS among patients admitted to the emergency department of a tertiary hospital.
Methods : We conducted a post-hoc analysis of a single-center prospective observational study of all patients
admitted to our emergency department between April 2003 and March 2014. The diagnosis of TTS was basedon the Mayo diagnostic criteria.
Results : Among 14,178 patients admitted, TTS was diagnosed in 33 patients (male, 36 ％ ; median age 76 (inter­
quartile range, 70-80) years), with a prevalence rate of 0.23 ％. The cases without preceding physical illness
included 40 ％ of patients (the primary TTS group), and the cases with preceding physical illness included 60 ％of patients (the secondary TTS group). Chest discomfort was the presenting symptom in only 25 ％ of patients inthe secondary TTS group compared to 92 ％ in the primary TTS group (p＜0.001). The Acute Physiology andChronic Health Evaluation II scores were higher in the secondary TTS group than in the primary TTS groups(p＝0.002)
Conclusions : The prevalence of TTS among patients admitted to the emergency department was 0.23 ％. TTS
triggered by a physical illness formed a high percentage, and in the majority of these cases chest symptoms
were not presenting complaints. Nevertheless, physicians should screen for TTS as part of the assessment ofpatients admitted to the emergency department. Shinshu Med J 70 : 39―46, 2022
(Received for publication May 10, 2021 ; accepted in revised form October 8, 2021)
Key words : Takotsubo syndrome, emergency department, chest symptom

Ⅰ Introduction

often preceded by an emotional or physical trigger3）4）.
Although TTS is generally transient in nature, re­Takotsubo syndrome (TTS), which was first de­quiring only supportive management4）, complications

scribed in 1990, is an acute, reversible disorder of theof TTS, such as heart failure, arrhythmias, and someheart that is characterized by left ventricular dys­

hemodynamic instability, can be life-threatening or. Chest pain and dyspnea, mimicking an

prolong hospital stay5）6）. Menopause and severe emo­

acute coronary syndrome, are common clinical mani­tional or physical stress are known risk factors forfestations of TTS. In addition, the onset of TTS is

TTS2）-7）, although absence of these factors does not

function1）-3）

preclude the diagnosis of TTS. Therefore, improved＊

Corresponding author : Hiroshi Imamura
Department of Emergency and Critical Care Medicine,
Shinshu University School of Medicine, 3-1-1
Asahi, Matsumoto, Nagano 390-8621, Japan
E-mail : imamura@shinshu-u.ac.jp

No. 1, 2022

understanding of TTS is essential for diagnosis andtreatment.
TTS complicates the clinical course of various dis­eases. However, few reports have evaluated the preva­
39

Yashio・Imamura・Mochizuki et al.

lence of TTS among patients hospitalized for an a-disease ; (3) new abnormality on the ECG, either ST-

cute condition in the United States and among thosesegment elevation and/or T-wave inversion, or a

7）
-10）

. It is pos­modest elevation in cardiac troponin ; and (4) absence

sible that TTS might be specifically prevalent amongof pheochromocytoma, myocarditis, or subarachnoid

patients presenting to the emergency department.

hemorrhage.

admitted to the intensive care unit (ICU)

Considering the few studies that have addressed this

These data were then used to estimate the preva­

issue, we aimed to clarify the prevalence of TTS

lence of TTS among patients admitted to our emer­

among patients admitted to the emergency depart­gency department. To describe the range of clinicalment of a tertiary hospital, and to describe the clinicalfeatures of TTS, patients with a positive diagnosis

characteristics of TTS among these patients.

were divided into two groups according to the exis­
tence of preceding physical illness : the Primary TTS

Ⅱ Methods
Ａ

group, in which TTS was the main event of hospital­
ization, and the Secondary TTS group, in which

Study design
The study was approved by the Shinshu University

another physical illness was the main cause of hospi­

School of Medicine Institutional Review Board andtalization and TTS was recognized as a complication.

was conducted in accordance with the amended Dec­

Clinical features were compared between these twolaration of Helsinki.

groups.

This was a post-hoc analysis of a prospective ob­ＣStatistical analyses

servational study of all patients admitted to theContinuous variables are reported as median (in­emergency department of Shinshu University hospitalterquartile range), with categorical variables reported

between April 2003 and March 2014. Shinshu Uni­as count and percentage. Between-group comparisonsversity hospital is an academic tertiary hospital locat­

of continuous variables were performed using the t-

2

ed in the Matsumoto region (area 1,868 km , 430,000

test for normal and non-normal variable distributions,residents) and is also the base hospital for the physi­

and a chi-squared analysis (χ 2) was used to compare

cian-staffed helicopter emergency medical service

categorical variables. Analyses were performed using

2

for Nagano prefecture (area 13,560 km , 2 million resi­
11）

dents) .
Ｂ

Procedures
All patients presenting with one or more of the

IBM SPSS Statistics software (version 22), with a pvalue＜0.05 considered significant.
Ⅲ

Results

following findings underwent echocardiography to

Between 2003 and 2014, 14,178 patients were ad­screen for TTS : chest symptoms, abnormal electro­

mitted to our emergency department, with TTS di­cardiogram (ECG), pulmonary edema, or hypotension

agnosed in 33 cases, with a prevalence rate of 0.23 ％.

of unknown etiology. Unless contraindicated, all pa­

Of the 33 cases, 28 underwent coronary angiography.

tients underwent coronary angiography. The diagno­

Although 3 cases had shown significant stenosis andsis of TTS was made based on the Mayo diagnostic

received percutaneous coronary intervention, the dis­4）

criteria , as follows : (1) transient left ventricular sys­

tribution of asynergy did not correspond to the dom­

tolic dysfunction, which is typically regional and ex­inant region of the coronary artery with significant

tends beyond a single epicardial coronary distribu­

stenosis in each case. A coronary spasm was not ob­

tion ; (2) absence of obstructive coronary disease or

served in any case. In addition, 5 cases did not un­angiographic evidence of acute plaque rupture, not­dergo coronary angiography owing to the patients’

ing that the diagnosis of takotsubo cardiomyopathy

conditions (head injury, cardiopulmonary arrest after

can still be made in the presence of coronary disease

epidural anesthesia, pan peritonitis, snake bite, airway

so long as the abnormal contractile motion of the

obstructions). ECG abnormalities were observed in allheart wall is not in the distribution of the coronary

the cases at TTS diagnosis : ST elevation (39 ％), T

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Shinshu Med J. 70

Takotsubo syndrome among ED patientswave inversion (48 ％), abnormal Q wave (24 ％), andmarized in Table 3. Complaints of chest symptoms

poor R wave progression (18 ％). Autumn is the mostwere more frequent in the Primary TTS groups

prominent season for the onset of TTS, as follows :(92 ％) than in the Secondary TTS group (25 ％) (p＜spring (21 ％ ), summer (15 ％ ), autumn (39 ％ ), and

0.001 ; Fig. 1). Therefore, while chest symptoms were

winter (24 ％). The baseline characteristics of these

the clinical clue for TTS in most of patients in thepatients are summarized in Table 1. Among thisPrimary TTS group, the diagnosis for the Secondarygroup, 64 ％ were female and 76 ％ had a history of

TTS group was based on objective findings of pul­

hypertension. A physical triggering event was identi­

monary edema, ECG abnormality, arrhythmia, or un­

fied in 20 of these 33 cases (the secondary TTS
group), and the other 13 cases were classified in thePrimary TTS group. The triggering events among
patients in the Secondary TTS group included thefollowing : hypoglycemic coma ; acute on chronic
renal failure induced by acute diarrhea ; epilepsy ;bacterial infection, including sepsis, acute upper re­
spiratory tract infection ; bowel obstruction ; asthma
attack ; superior mesenteric artery obstruction ; head
injury ; snake bite ; airway obstruction ; pan perito­
nitis ; elective hepatectomy ; and epidural anesthesia.
The triggering events among the Primary TTS groupwere emotional stress (6 cases) or unknown (7 cases) ;emotional stress included inter-personal quarrels, thedeath of a spouse, and work-related stress. The
baseline characteristics of patients in each of these 2groups are summarized in Table 2.
The clinical course for each of the 2 groups is sum­Table 2

Baseline characteristics of patients with TTS
Characteristics

Number of patientsAge (years)
Female, n (％)
BMI (kg/m2)
Medical history, n (％)
Hypertension
Dyslipidemia
Diabetes mellitus
Smoking
Psychiatric disease
Cardiac failure
Medication on admission, n (％)
Beta-blocker
ACE inhibitor/ARB
Calcium channel blocker
Diuretics
Steroid33
76 (70-80)
21 (64)22.4 (19.2-25.1)
25 (76)
10 (30)8 (24)
4 (12)
3 (9.1)6 (19)3 (9)
20 (61)14 (42)
11 (33)3 (9)BW, Body Weight ; BMI, Body Mass Index ; ACE, Angiotensinconverting Enzyme ; ARB, Angiotensin II Receptor Blocker

Baseline characteristics of each TTS group

VariableAge (years)
Female, n (％)
BW (kg)
BMI (kg/m2)
Medical history, n (％)
Hypertension
Dyslipidemia
Diabetes mellitus
Smoking
Psychiatric disorder
Cardiac failure
Medication on admission, n (％)
Beta-blocker
ACE inhibitor/ARB
CCB
Diuretics
Steroid

Table 1

GroupsP-valuePrimary(n＝13)

Secondary(n＝20)

77 (70-80)
10 (77)52.0 (42.5-60.2)
24.1 (20.2-25.9)

76 (70-81)
11 (55)51.5 (45.9-57.8)
21.0 (19.2-24.3)

0.446
0.278
0.824
0.877

12 (92)2 (15)1 (8)1 (8)2 (15)1 (8)

13 (65)8 (40)7(35)
3 (15)
1 (5)
5 (25)

0.108
0.245
0.108
1
0.547
0.361

0 (0)
10 (77)5 (38)
3 (23)0 (0)3 (15)
10 (50)9 (45)
8 (40)
3 (15)

0.261
0.159
1
0.456
0.261

BMI, Body Mass Index ; ACE, Angiotensin-converting Enzyme ; ARB, Angiotensin II Receptor Blocker ; CCB, Calcium channel blocker
No. 1, 2022

41

Yashio・Imamura・Mochizuki et al.
Table 3Presentation and clinical course of each group of TTS

Variable

Chest symptoms on presentation, n (％)
Chest pain
Dyspnea
No chest symptomFirst clue to diagnosis,n (％)
Pulmonary edema
ST change in ECG
Arrhythmia
Hypotension
APACHE Ⅱ score
Peak CK-MB (IU/L)CRP (mg/dL)
BNP (pg/mL)
Anatomical variants of TTS, n (％)
Apical typeNon-apical type
Ejection Fraction at diagnosis
Treatment device, n (％)
Mechanical ventilation
IABP
Temporary pacing
Hospital stay
ICU stay
Complication, n (％)
Arrhythmia
Embolism
Cardiac rupture
Death, n (％)

GroupsP-valuePrimary(n＝13)

Secondary(n＝20)

12 (92)10 (77)2 (15)
1 (8)

5 (25)
2 (10)
3 (15)
15 (75)＜0.001＜0.001
1＜0.0010
2 (15)00
9 (7-11)29 (17-51)
0.4 (0.2-1.3)
234.0 (138-443)

6 (30)
5 (25)
2 (10)
2 (10)
17 (14-21)
24 (14-34)
4.8 (0.1-11.7)
858 (527-1577)

0.060
0.676
0.508
0.508
0.002
0.135
0.006
0.539

13 (100)045 (40-63)

20 (100)0†40 (36-49)＊＊＊

2 (15)0
1 (8)
11 (8-15)
5 (3-6)

11 (51)0
2 (10)
25 (22-34)
12 (4-25)

0.032

2 (15)000

10 (50)
0
0
1 (5)

0.067

＊＊＊

0.198
＊＊＊

1
0.018
0.006
＊＊＊
＊＊＊

1

ECG, Electrocardiogram ; APACHE, Acute Physiology and Chronic Health Evaluation ; CK, Creatine Kinase ;CRP, C-Reactive Protein ; BNP, Brain Natriuretic Peptide ; IABP, Intra-aortic Balloon Pumping ; ICU, Intensive Care Unit†
Three cases were excluded due to missing values.

Fig. 1 The number of patients, withand without chest symptoms, ineach of the two TTS groups

explained hypotension. The Acute Physiology andof ICU and hospital stay. The occurrence of arrhythmia

Chronic Health Evaluation (APCHE) II scores were(including torsades de pointes, complete atrioventric­

higher in the Primary TTS group than in the emo­ular block, atrial fibrillation, bradycardia, ventriculartional and unknown trigger groups, as was the lengthtachycardia, paroxysmal supraventricular tachycardia,

42

Shinshu Med J. 70

Takotsubo syndrome among ED patientsand multifocal premature ventricular contraction)

tional Classification of Diseases (9th revision). The

also tended to be more frequent in the Secondary

prevalence of TTS in our study was about 10-fold

TTS group. Temporary pacing was required for 3

higher than the rate reported by Deshmukh et al.

cases (2 cases for complete atrioventricular block and

The following two reasons might provide an explana­1case for torsades de pointes), while the other cases

tion for this discrepancy. First, Deshmukh et al.

were only followed up. One patient in the physicalstudied all hospitalizations, including non-emergencygroup died due to multiple organ failure subsequentpatients, while our study was performed at a tertiary

to obstruction of the superior mesenteric artery.

emergency department ; thus, the severity and theurgency of illness were higher among our study

Ⅳ Discussion

group than the patients in Deshmukh et al.’s study.

The main findings of our study were as follows : (1)As such, it is possible that our study patients were ina prevalence rate of TTS of 0.23 ％ among patientsa more stressful situation. Second, in our study, alladmitted to a tertiary emergency department ; (2)patients with chest symptoms, abnormal ECG, pul­

triggering of TTS by physical illness (the Secondary

monary edema, or hypotension of unknown etiology

TTS group) in 60 ％ of patients ; and (3) absence ofunderwent an echocardiogram assessment. In thischest symptoms (pain and dyspnea) in the majority

way, almost all patients with TTS would have beenof cases of TTS triggered by physical illness. To ouridentified ; in contrast, Deshmukh et al. calculated theknowledge, this is the first report regarding the prev­

prevalence rate of TTS from a database of patientsalence of TTS among a general group of patients ad­in daily practice. As a complication of various physi­

mitted to the emergency department.

cal illnesses, TTS would be especially difficult to di­1）

TTS was first described in Japan in 1990

and isagnose in clinical practice. Thus, a considerable num­characterized by a transient regional systolic dys­

ber of patients with TTS may have been overlookedfunction of the left ventricle, with four types of ana­

in Deshmukh et al.’s study7）. In ICUs, the prevalence

tomical variants based on the abnormality in therate of TTS has been reported to range between

12）: apical type,

0.9 ％ up to 26 ％8）9）16）17）. More recently, it has been

mid-ventricular type, basal type, and focal type. Al­

suggested that TTS may be associated with severe

though the practical significance of these anatomical

conditions that cause high sympathetic activity, suchdifferences has not been fully clarified, it is possible

as sepsis, respiratory failure and neurological emer­that each represents the different time periods need­

gencies10）15）18）. As such, TTS may be more frequent

ed for recovery of the affected left ventricular seg­among patients admitted to the ICU than in generalmotion of the left ventricular wall13）

ments . Pathophysiologically, TTS is related to sym­10）13）

pathetic activation and catecholamine toxicity.

emergency settings. Because TTS can adversely
influence the clinical course of primary diseases, phy­

The prevalence rate of TTS among patients withsicians should recognize the prevalence of TTS insuspected acute coronary syndrome is 1-3 ％4）-7）14）15）.

each clinical setting and diagnose it as soon as possi­

But the prevalence of TTS among the general popu­

ble.

lation, as well as among the general population of

TTS has recently been classified into primary andpatients admitted to the emergency department, hassecondary subtypes. In primary TTS, patients seekreported a preva­

care for acute cardiac symptoms18）. By comparison,lence rate of TTS of 0.02 ％ among all acute hospital­

secondary TTS develops in patients who are alreadyizations in the United States. Their data were collect­

hospitalized for another problem, such as peri-

ed from the inpatient care database of nearly 1,000

operative complications, trauma, or other medical

hospitals in the United States. Specifically, 6,837 pa­

conditions. Our study also classified TTS along withtients among 33,506,402 hospitalizations received athese subtypes. As the study was performed in the

primary diagnosis of TTS, as coded by the Interna­

emergency department, most cases of secondary

been unclear. Deshmukh et al.

No. 1, 2022

7）

43

Yashio・Imamura・Mochizuki et al.

TTS were diagnosed upon admission among patientsnosis in the majority of cases in the Secondary TTS

in the physical group.

group. Therefore, TTS should be considered, with a
19）

A 2014 meta-analysis

estimated a prevalence rateof primary TTS of 60 ％, with a 40 ％ rate of second­high index of possibility, among patients presenting
with these symptoms.

ary TTS. Among our study group, the rate of sec­

Early recognition of TTS among emergency pa­

ondary TTS was higher than this, at 60 ％. It mighttients is important when we consider the potential

be that this higher prevalence rate of secondary TTS

for TTS to complicate the clinical course of a widereflects our increased awareness and, thus, diagnosis

range of illnesses. Thus, echocardiography should beof this condition.

repeated in patients presenting with an abnormal

The high prevalence of TTS among post-meno­
18）

ECG, pulmonary edema, or hypotension of unknown

pausal women has been well documented . In their

etiology, which are known complications of TTS. In

review of patients diagnosed with TTS among 31

addition, point-of-care ultrasonography, which con­heart institutes in Germany and Austria, Schneider

sists of a focused cardiac ultrasound examination

et al.20） reported that 91 ％ of patients with TTS were

performed by a physician at the time of the physical

women. Moreover, physical stress as a cause of TTS

examination, would provide a feasible solution for

was more frequent in men (57 ％ ) than in womenearly recognition of ultrasound-specific signs of(30 ％), with women experiencing greater emotional

TTS22） and thus, screening for TTS.

triggers or unknown triggers of TTS. This is consis­

A previous study reported a higher APCHE II

tent with our findings. In our study group, 64 ％ ofscore among patients with TTS associated with acutepatients were women. In the Primary TTS group,

medical stress or surgery/procedure than among

77 ％ of patients were women, with TTS in men com­those with an emotional stress triggering event23）.

monly having a physical trigger.

Similarly, patients in the Secondary TTS group had

Previous studies have reported chest pain as being

significantly higher APACHE II scores than patientsthe presenting symptom in 41-75 ％ of TTS cases12）in the Primary TTS group in our study. Further­

19）
21）

, this rate being consistent with our rate of 51 ％more, the occurrence of arrhythmia was more fre­for our study group. Of note was that chest pain wasquent in the Secondary than in the Primary TTS

the presenting symptom in only 25 ％ of patients ingroup. Therefore, cardiac damage by TTS is likely to

the Secondary TTS group. The reason for this dis­be greater in the secondary than in the primarycrepancy between groups is unclear, although thegroups due to higher sympathetic activity and cate­majority of patients in the Secondary TTS group had

cholamine levels. It has been reported that TTS in­a critical physical illness, including some with alteredcreases the risk of mortality in the ICU16）23）24）. Thus,

consciousness. As these cases were critical, the per­it is possible that emergency patients with physicalception of chest pain may have been attenuated byillness and concurrent TTS would be at an increased

the health condition. For example, among the pa­

risk of a poor clinical outcome, particularly with atients with pulmonary edema, we observed one casedelay in TTS diagnosis. Moreover, early diagnosis ofeach of hypoglycemic coma (unable to complain), epi­

TTS is essential for proper hemodynamic manage­

lepsy (unable to complain), and acute obstructive

ment and could improve the prognosis of emergency

suppurative cholangitis (chest discomfort would bepatients.

masked by other symptoms such as upper abdomi­
nal pain). Therefore, while chest symptoms were theⅤ

Limitations

clinical clue for a diagnosis of TTS in the majority of

The limitations of our study were as follows. First,

patients in the Primary TTS group, objective findings

this was a single-center study performed in a tertiary(such as pulmonary edema, hypotension, ECG abnor­

emergency department. Although we included almost

mality, or arrhythmia) were the clinical clue for diag­

all patients, regardless of the nature of the medical

44

Shinshu Med J. 70

Takotsubo syndrome among ED patients

condition, the severity of illness could have been

ent hospitals.

higher in our study population of patients admittedⅥ

to the emergency department than in primary care

Conclusions

facilities. Thus, the frequency of TTS could vary

The prevalence of TTS among patients admitted

between facilities according to the severity of patientsto a tertiary care center was 0.23 ％. The majority ofadmitted to their services. Second, the number ofpatients with TTS triggered by physical illness (sec­patients with TTS in each group was relatively small.

ondary TTS) did not present with chest symptoms,

Thus, differences in clinical features of primary andwith objective findings, such as pulmonary edema

secondary TTS could not be fully clarified. A multi­

and ECG abnormality, being major clues to TTS di­center study would be ideal for the population andagnosis. Therefore, physicians should consider

averaging the severity ; however, it is not feasible forscreening for TTS in the assessment of patients ad­

all suspected patients to be screened TTS with echo­mitted to the emergency department.

cardiography to the same high quality among differ­
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