Vol.2, No.4, 300-305 (2010) Health
doi:10.4236/health.2010.24044
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
S tress cardiomyopathy: clinical features and outcomes
Lilian Hamity 1, Franco Ramel lo1, Leandro Marani 1, Alejandro Moyano1, Eduard o Moreyr a2,
Luis E. Alday1
1Hospital Aeronáutico Córdoba, Córdoba, Argentina;
2Professor of Medicine, Universidad Nacional de Córdoba, Córdoba, Argentina
Received 6 January 2010; revised 25 January 2010; accepted 29 January 2010.
ABSTRACT
Objectives: To establish the prevalence, clinical
features, and outcomes of the recently recog-
nized stress cardiomyopathy whose physiopa-
thology is still not completely clarified. Material
and methods: The prevalence and clinical find-
ings of stress cardiomy op athy were assessed in
a group of 378 patients undergoing cinecoro-
nariography for acute coronary syndromes dur-
ing a 7-year period. The inclusion criteria were
severe chest pain, ischemic electrocardiogra-
phic changes, reversible left ventricular dys-
hypokinesia, and normal coronary arteries.
Eight patients, 7 female (2.1% of all patients and
5.0% of the women), with a mean age of 65.3 ±
8.5 years fulfilled the requirements. Results: The
precipitating factor was severe stress in all of
them. Cardi ac enzymes were slightly raised. Th ere
was apical le ft ven tric ular dy skin esi a i n 6 patients,
midventricular in another, and diffuse hypokine-
sia in the remaining. One patient showed mod-
erate mitral regurgitation. The response to con-
ventional treatment and patient outcomes were
favorable in all cases with prompt reversal of
the left ventricular dyskinesia as assessed by
echocardiography. There were 4 recurrences, 2
requiring readmission to hospital, despite con-
tinuous treatment with combined alfa and beta
adrenergic blockers and calcium antagonists.
Conclusions: In our hospital, stress cardiomyo-
pathy had a prevalence of 2.1% in all patients
with acute coronary syndromes and 5.1% in
women and should be considered in their dif-
ferential diagnosis, especially in middle aged
female p atient s with a history of sev ere previous
stress. There was a favorable outcome but re-
currences may occur despite uninterrupted me-
dical treatment following discharge.
Keywords: Stress Cardiomyopathy; Takotsubo
Syndrome; Myocardial Ischemia; Cardiomyopathy
1. INTRODUCTION
The recently described stress cardiomyopathy (SCM),
resembles an acute coronary syndrome (ACS) presenting
with severe chest pain, left ventricular dys- or hypokine-
sia not following a determined pattern corresponding to
a single involved artery as it occurs in acute myocardial
infarction.
It was first described in Japan in the early 90’s as “ta-
kotsubo syndrome” (from tako: octopus, tsubo: trap) for
the similarity with the narrow necked and large rounded
bottom fishing pots used in Japan to trap octopus, with
the angiographic left ventricular systolic appearance in
affected patients [1]. Other names proposed for this
syndrome are “apical ballooning syndrome”, “broken
heart”, “transient myocardial stunning”, and “transient
apical dyskinesia” [2-8]. The syndrome occurs almost
exclusively in middle aged women with a clinical onset
usually following an episode of severe emotional stress
although it may occur during the course of an illness,
after some kind of surgery, or even without any provok-
ing factor [3,9]. There is a varying severity, with risk of
arrhythmias, congestive heart failure, shock and even
death. The left ventricular kinetic ab normalities are tran-
sient with full recovery of the contractility in about 2
months along with normalization of the electrocardio-
graphic ischemic changes in a variable period of time.
The incidence of recurrences has been estimated around
11% in a group of 100 patients in a 4-year follow-up
period [10].
In this study we analyze the features and frequency of
SCM in a group of consecutive patients with ACS re-
quiring selective coronarographic study (SCG) during a
7-year period in a general hospital.
2. METHODS
We performed a retrospective-prospective, observational
study to determine the frequency of SCM, as already
defined, in all patients studied by SCG for ACS from
March 2002 to February 2009. In clusion cr iteria were: a)

L. Hamity et al. / Health 2 (2010) 300-305
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301
severe, oppressive, chest pain, b) ischemic ECG changes,
c) creatin phosphokinase (CPK) enzyme elevation, d)
normal or no significant lesions in the coronary arteries,
and e) left ventricular dys- or hypokinesia. There were
378 consecutive patients with ACS undergoing SCG, of
which 238 (63%) were males . The mean age was 67.8 ±
9.6 years. Eight patients, 7 of them women, fulfilled the
inclusion criteria. Serial laboratory studies, EKG’s, and
transthoracic color Doppler echocardiograms were per-
formed while admitted at the coronary care unit. They
were treated according to current guidelines for the
management of ACS’s. Following discharge, patients
continued tailored medical treatment in k eeping with the
accompanying risk factors. The left ventricular contrac-
tility was assessed by echocardiography. In case of re-
currences, patients were studied and treated as in the first
admission. The mean follow-up period was 3.8 ± 2.1
years. The continuous variables were expressed as mean
± SD or median with its range.
3. RESULTS
The 8 affected patients made up 2.1% of all patients with
ACS with an incidence for women of 5.0%, while the
mean age was 65.3 ± 8.5 years. All of them presented to
the Emergency Department with severe oppressive chest
pain lasting more than 10 min utes. The precip itating fac-
tor in all patients was always a severe episode of emo-
tional stress as a result of diverse causes. All patients had
electrocardiographic signs of acute ischemia. In 7 of
them, there were anterior wall negative T waves and in
only one there was infero-lateral ST segment elevation.
(Figure 1) The QTc interval was transiently prolonged
in all cases with a median of 475 msec (range 464-490).
The CPK was also mildly elevated in all patients with a
median of 290 u/100 ml (range 220-390). Echocardio-
graphic studies showed segmental contractile left ven-
tricular parietal abnormalities in 7 cases and generalized
hypokinesia in the remaining. SCG was always per-
formed in the acute phase, no longer than 48 hou rs from
the onset of symptoms but for the patient with ST eleva-
tion that was initially treated with thrombolysis, and had
the study done for recurrence of chest pain on the 5 th day
after admission. No patient showed significant coronary
artery obstructions. Nevertheless, the left ventricular an-
giographies showed myocardial dys- or hypokinesia with
decreased ejection fraction. There was apical dyskinesia
in 6 (Figure 2), mid-ventricular involvement in one,
associated with mild mitral incompetence, and the last
patient had generalized hypokinesia. A summary of all
clinical and laboratory findings is shown in Table 1.
The median length of stay in hospital was 6 days
(range 4 to 10). As already mentioned, treatment was
according to the guidelines for ACS’s with nitrites,
heparin, aspirin, alpha and beta adrenergic blockers
agents, vasodilators, and analgesics as required. Follow-
ing discharge, they were put on adrenergic blockers or
calcium antagonists as decided by the personal physician.
Besides, they received aspirin, statins, and associated
risk factors were addressed (Table 1).
There were 4 recurrences but only 2 required readmis-
sion 8 and 18 months following the first episode. All had
inadequate control of anxiety disorders. Severe stress was
the precipitating factor. The 2 readmitted patients repro-
duced the initial symptomatology undergoing the same
diagnostic and therapeutic measures, again with favor-
able outcomes. The SCG showed similar findings to the
initial study.
Table 1. Clinical and ancillary findings. (AW: anterior wall; BMI: body mass index; ILW: infero-lateral wall; LV: left ventricular; D:
dyslipidemia; EF: ejection fraction; SH: systemic hypertension)
Patient Age Sex
Stress trig-
ger EKG ST & T changes QTc (msec)CPK (u/100 ml) Associated risk factors LV EF & dys- function
A 46 Female
Conjugal
quarrel Negative T waves AW 484 271
BMI > 25
SH - D 0.36, global
B 49 Female
Laboral
stress ILW ST elevation 480 311
BMI > 25
Diabetes 0.57, apical
C 64 Female
Family
argument Negative T waves AW 478 264
BMI > 25
SH - D 0.56, apical
D 62 Female Infidelity
Negative T
waves AW 469 220
BMI > 25
SH - D 0.58, mid-ventricular
E 65 Female
Spouse’s
terminal
illnes
Negative T
waves AW 468 253 SH - D 0.55, apical
F 56 Female Job loss
Negative T
waves AW 464 276 Smoking 0.51, apical
G 59 Male
Laboral
problems Negative T waves AW 470 340 Smoking 0.45, apical
H 73 Female
Distressful
disease Negative T waves AW 490 390
SH – D
Smoking 0.50, apical

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(a) Admission EKG (patient E)
(b) EKG of same patient at discharge
Figure 1. (a) Admission EKG of patient E showing deeply negative T waves in the
anterior wall and prolonged QT interval; (b) EKG of same patient at discharge with
normalization of repolarization abnormalities.
Figure 2. Left ventriculography of patient G in systole and diastole showing typical apical bal-
looning.

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4. DISCUSSION
The findings in our study in pa tients with SCM mirrored
those described in papers following the original descrip-
tion of the syndrome in Japan in the early 90’s [1]. The
involved populatio n was mainly middle aged females [2].
The chest pain at presentation was indistinguishable
from that occurring in ACS and always precipitated b y a
severe stress episode [9]. The EKG showed acute ische-
mic changes, usually anterior wall T wave inversion with
lengthening of the QTc interval, accompanied by small
rise of the myocardial markers (the CPK enzyme in our
study) [2,10]. We did not find abnormal Q waves on the
EKG though they may also transiently happen [2].
SCG ruled out the presence of significant coronary
stenoses while apical left ventricular dyskinesia oc-
curred in 7 patients with extension to the midventricu-
lar region in one of them. In the remaining patient there
was generalized hypokinesia [12]. One patient also had
moderate mitral regurgitation, which with the left ven-
tricular contraction abnormalities were transient [13].
Response to ACS treatment was favorable without
major complications resulting in short length of stay.
Among them, arrhythmias, heart failure, shock, and
very rarely inhospital death have been described [2,9,
12]. Several risk factors were present in all cases and
were addressed according to current recommendations.
Despite continuous medical treatment following dis-
charge, there were 4 mid-term recurrences, 2 requiring
readmission to hospital, with similar course to the ini-
tial presentation. Anxiety disorders were more difficult
to control in patients with recurrences as compared to
those without them. In one study, the frequency of re-
currences was around 11%. Patients at risk could not be
identified and adrenergic beta blocker therapy did not
prevent them [10].
Prevalence of SCM has been estimated in about 2%
of patients presenting with ACS and 3 times higher if
just women are considered. We had a somewhat similar
occurrence (2.1 and 5.0%, respectively). According to
these figures the diagnosis of SCM should be borne in
mind in patients with ACS in any of both situations.
[5,9,14]. Increased recognition of this syndrome is re-
flected in the higher number of publications in recent
years.
Since the physiopathogenesis of SCM has still not
been elucidated several theories have been proposed.
There is widespread agreement that an excess of cir-
culating catecholamines would cause the observed de-
rangements through different mechanisms. [4] The oc-
currence of spasm of the epicardial coronary arteries was
initially propo sed and th en microcircu latory dysfun ction.
[1,9] However, both were discarded since the dyskinetic
territory was more extensive than that corresponding to
the perfusion of just one artery and it was not clear whe-
ther the microcirculatory dysfunction was the cause or
the consequence of SCM. [16] On the contrary, other
authors suggested, based on laboratory studies showing
higher levels of catecholamines in SCM than in similar
control patients with myocardial infarction, a direct my-
ocardial damage. Furthermore, patients undergoing en-
domyocardial biopsy, showed monocyte inflammatory
infiltrates and myocytolysis similar to those occurring in
excess catecholamine myocardial damage. [17] More
recently, it has been proposed that high level circulating
catecholamines would trigger an intracellular signaling
pathway that would change the stimulating protein G
function to inhibiting protein G in beta 2 receptors. Al-
though this change would serve as a protecting mecha-
nism against cell apoptosis mediated by intensive activa-
tion of beta 1 receptors, it would also produce a negative
inotropic effect in cardiomyocytes. The higher apical left
ventricular adrenergic receptor density would explain
why this region is the most frequently affected in SCM
while the basal segments are usually spared. Adreno-
receptor distribution individual phenotypes in SCM pa-
tients would explain the different left ventricular re-
gional involvement. [7] Accordingly, less frequent left
ventricular hypo-dyskinesias like the midventricular,
generalized, and the inverted “takotsubo” affecting basal
contractility but sparing the apex might occur [18,19].
On the other hand, in a recent review of all types of
SCM, Bybee and Prasad proposed on the basis of expe ri-
mental studies, that excessive stress would activate the
right cortical insula and the ipsilateral cerebral amigdala
stimulating the autonomic nervous system, producing a
local excess of catecholamines. At their tu rn, the y would
activate the calcium channels increasing the cytosolic
and mitochondrial calcium levels with release of free
radicals and lipid membrane peroxidation., resulting in
cell death and band contraction necrosis producing EKG
abnormalities and arrhythmias [12].
Some authors, though accepting the role of increased
catecholamine secretion as a triggering factor, suggest
that SCM would be instead an aborted “myocardial in-
farction”. It is hypothesized that coronary artery lesions,
unidentified by SCG because of their very small size,
would produce plaque accidents with spontaneous reso-
lution through endogenous fibrinolysis preventing an-
giographic recognition due to the time elapsed since on-
set of symptoms and performance of the study. SCM
would then be the consequence of previous myocardial
ischemia. Radioisotope studies using metabolic markers
have shown altered fatty acid handling and glycose
transportation probably caused by catecholamine excess
and calcium intracellular overload resulting in “myocar-
dial metabolic stunning” [20-22].
The cause of the more frequent occurrence of SCM in
menopausic women has not been elucidated. A gender
difference has been suggested or else, microcirculatory

L. Hamity et al. / Health 2 (2010) 300-305
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304
endothelial dysfunction facilitated by a decrease of es-
trogenic stimulation [5].
Dynamic left ventricular outflow tract obstruction has
also been described in SCM patients. [23] It is still not
clear if the gradient is the cause or a consequence of the
syndrome [16].
Finally, Akashi et al., based on experimental studies in
rats, propose that sudden, unexpected, stress, would ac-
tivate autonomic nervous system neurons with estro-
genic receptors causing higher release of catecholamines
that would stimulate vascular and cardiac adrenorecep-
tors resulting in systemic hypertension and increased
inotropism. The aforementioned higher expression of
apical adrenoreceptors, would be responsible of the dys-
kinesia at that level through the toxic effect on the car-
diomyocytes. The dynamic left ventricular outflow tract
obstruction present in some patients with SCM would be
caused by the basal myocardial hypercontractility. The
loss of estrogenic protection in the nervous system and
myocardium following menopause would exaggerate all
these disarrang ements [15].
The previous discussion shows that the origin and fa-
cilitating triggering factors of SCM are still under debate.
Since SCM description and better identification are re-
cent, it is still not clear which is the ideal treatment for
these patients in the acute phase and after discharge to
prevent recurrences. Nevertheless, supported by labo-
ratory animal experimental studies, Akashi et al., rec-
ommend combined alfa and beta adrenergic blockers
instead of individual administration. Calcium channel
antagonists and nitrites would also be effective [15].
5. CONCLUSIONS
The prevalence of SCM in a 7-year period in our hospi-
tal was 2.1% of all patients with ACS requiring SCG and
5.0% if just women were considered. There was an ini-
tial favorable outcome with satisfactory response to
conventional medical treatment though recurrences oc-
curred in patients with inad equate control in anx iety dis-
orders and 2 of them required readmission to hospital.
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