Takotsubo Cardiomyopathy Potential Differential Diagnosis in Acute Coronary Syndrome

1. TCM in ASC Diagnosis 1
TAKOTSUBO CARDIOMYOPATHY POTENTIAL DIFFERENTIAL DIAGNOSIS IN
ACUTE CORONARY SYNDROME
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2. TCM in ASC Diagnosis 2
Takotsubo Cardiomyopathy Potential Differential Diagnosis in Acute Coronary Syndrome
Introduction
Takotsubo Cardiomyopathy (TCM) came to light in Japan in 1990 and has since then
gained widerecognition all over the world. The term “takotsubo” comes from a Japanese
word referring to an octopus trap (Hurst et al., 2010). The trap bears a resemblance to the
apical bloating of the systole of the left ventricle in the early stage and dominant state of the
disease. TCM can be described as being an important differentiated form of diagnosis for
acute coronary syndrome (ACS). TCM is characterized by acute and reversible dysfunction
of the left ventricle often aggravated by intense physical and emotional stress (Bär et al.,
2009). Occasionally, although rarely, the ballooning of the right ventricle is also reported
(Haghi et al,. 2010).On the other hand, ACS refers to a range of clinical manifestations that
range from those associated with ST elevation myocardial infarction (STEMI) to those that
are found in non ST elevation myocardial infarction (NSTEMI)(Chlus et al., 2016). Usually,
it is associated with atherosclerotic plaque rupture or complete thrombosis(Chlus et al.,
2016). Researchers state that the exact pathogenesis of TCM is yet to be known, yet there are
various hypotheses that have been discussed to date and they include: Coronary artery spasm,
myocardial micro-infarction, myocardial stunning that is induced by raised catecholamine,
reperfusion injury and micro-vascular dysfunction (Yoshida et al., 2009; Guglin and
Novotorova,2011).
Takotsubo cardiomyopathy is a condition, which affects up to 2.2% of the population
in Japan and up to 3% of people in the European nations (Yoshida et al., 2009). It is more
prevalent in post-menopausal women,although younger men and women can be affected too.
The most common symptom that presents itself, in most cases, is chest pain which occurs in
70- 90% of those affected (Minhas, Hughey and Kolias, 2015). There are other symptoms
that are less common, such as pulmonary oedema and dyspnoea, which can occur in up to

3. TCM in ASC Diagnosis 3
20% of those suffering from TCM. It is very rare for cardiogenic shock, ventricular
arrhythmias and cardiac arrests to occur (Citro et al., 2010). There are also certain cases
where nonspecific symptoms may occur and they include weakness, cough, fever, and
syncope. TCM has attracted the attention of the medical world since it is considered as a
unique cardiomyopathy and has been seen as an important factor in the diagnosis of ACS. It
makes up an estimated 1 to 2% of the patients who show signs of ACS (Citro et al., 2010). It
is also understood that the estimate may be low due to elements associated with under
recognition. This assignment will take an in-depth look at TCM as a possible differential
diagnosis in ACS.
Though exhibiting relatively similar symptoms at their onset, Takotsubo
Cardiomyopathy and Acute Coronary Syndrome are two very distinct diseases. ACS is
caused by a sudden blockage of blood flow to some parts of the heart muscle, usually caused
by a blood clot(Kumar and Cannon, 2009). Depending on whether the blockage is partial or
complete, the effects may be either unstable angina or myopic infarct respectively(Kumar and
Cannon, 2009). When there is a complete blockage in the coronary arteries, the parts of the
heart muscle which receive blood from those specific arteries may die, a situation referred to
as infarction. The location of the blockage, the amount of time that blood flow is curtailed to
the specific parts of the heart and the amount of damage that occurs in that part of the heart
determines the type of ACS experienced. ACS can either be a myocardial infarction or an
unstable angina. TCM, on the other hand, is caused by an unusual inflation of particular parts
of the left ventricle. Depending on the ventricular part which experiences the inflation, TCM
can be described as apical, midventricular, basal or focal(Chlus et al., 2016). It is caused by
increased emotional or psychological stress and is most prevalent among postmenstrual
women, though it does occur among younger women and men as well, in very little
numbers(Chlus et al., 2016).

4. TCM in ASC Diagnosis 4
TCM has been described as a transient cardiac syndrome that does not show any
distinctive signs and symptoms, but whose manifestation often mimics that of ACS (Templin
et al.,2015). Since TCM often involves the left ventricular akinesis, just like some ACS, there
is the need to understand which of the two diseases is being diagnosed. Medical practice
provides evidence that TCM can appear like either NSTEMI or STEMI, yet they are managed
in different ways. In this regard, there are different electrocardiographic abnormalities that
have been determined, which can be important in differentiating TCM from NSTEMI and
STEMI without the presence of ST-elevation (Citro et al., 2009). The fact that TCM can
mimic ACS, means that it is important to rule out a differential diagnosis to come up with the
most appropriate strategy for treatment and more attention should be given to patients during
the acute phase of the syndrome. TCM has imaging characteristics that are important when it
comes to the process of its diagnosis. Although, there is no definite criterion in diagnosing
TCM, Mayo Clinic suggestedcriteria in 2004 which was again revised in 2008(Chlus et al.,
2016). All of these criteria must be present in diagnosing the syndrome; the presence of
stressors prior to the onset of symptoms, abnormalities on ECG reading must be noted in
comparison to the ECG of a normal heart, the levels of cardiac biomarkers must be raised or
abnormal and the patient must completely recover and function normallywithin a short period
of time (Madhavan et al.,2011). However, the above mentioned criteria cannot always be
followed and has several limitations. It is, therefore, necessary to create the common criteria
around the world for diagnosing TCM.
There are cases when a patient may experience acute chest pain, which may be caused
by ACS or TCM. ACS, as a term, involves a range of conditions which may not be easily
distinguished from TCM (Ghadri et al., 2014). Such conditions include STEMI, NSTEMI and
unstable angina. There are different guidelines that have been provided by National Institute
of Care Excellence (NICE), on stable angina and NSTEMI, which help in the early

5. TCM in ASC Diagnosis 5
management of the condition, before one is discharged from the care facility. Although
history and assessment may provide clues to a possible emotional or physical trigger, if one
exists. First, it is important to check whether the patient has chest pain and, if they are pain-
free, it is important to check when the last episode of pain occurred. The health care
practitioner has to determine whether the pain in question is cardiac related, or not, through
taking into consideration the history of chest pain, cardiovascular risk factors and history of
ischemic heart disease(Kumar and Cannon, 2009). It is also important to assess the patient for
any symptoms that may be indicative of ACS (Hurst et al., 2010). Such include pain in the
chest and other areas and pain in the chest that is associated with vomiting, hemodynamic
instability and severe sweating. At the same time, it is advisable that patients with chest pain,
without raised troponin levels, should be reassessed to determine whether the chest pain that
they experience is cardiac. In any case, where TCM is suspected, it is important to follow the
procedure of managing chest pain (Pelliccia et al., 2015). Therefore, the care provider is
expected to make use of their clinical conclusions to carry out further examination that is
diagnostic in nature. These symptomology would alert urgent clinical assessment and rapid
acquisition of resting ECG. These results of the findings should activate an ACS treatment
pathway in accordance to European Society of Cardiology (ESC) guidelines, wherein urgent
coronary angiography is indicated.
When a patient has normal ECG with possible ACS and at the same time has no
history of CAD and has normal troponin levels in the blood, it is advisable that the patient is
initially taken through coronary CT angiography, to have an assessment of the anatomy of the
coronary artery (Sharkey et al., 2010). This is referred to as level of evidence A. Level of
evidence B can be performed through myocardial perfusion imaging through technetium 99
m so that myocardial ischemia can be excluded (Sharkey et al., 2010). It is possible to
determine the difference in diagnosis of ACS and TCM due to significant differences in

6. TCM in ASC Diagnosis 6
inverted T waves. T waves’ inversion in precordial leads can suggest severe ischemia under
the left ventricular wall; this can be attributed to critical stenosis of the LAD (Hoyt et al.,
2010). Yet such observations have also been determined under the TCM which has new
electrocardiographic abnormalities. Different strategies that have been applied, with the aim
of differentiating ACS from TCM and one such tool is the electrocardiogram (ECG), which
shows anomalies in more than 95% of patients with TCM, during the acute phase of the
syndrome (Pilgrim & Wyss., 2008). According to Delgado et al (2011) there is a variation in
presentation of the electrocardiogram in patients with TCM. It is shown that ST-segment
elevation is evident in one-third of the patients and the anterior lead is most common, in such
cases. However, one can see the T-wave inversion as well as ST-T wave variations that are
nonspecific (Delgado et al., 2011). The use of electrocardiogram may indicate certain
changes that are seen during the acute phase of the syndrome such asdeep symmetric T wave
inversion and prolonged QT interval are present in more than 90% of TCM cases(Pilgrim and
Wyss, 2008). This may even take some months to resolve. Even though the long QT is
evident, torsades de pointes in most cases is hardly reported. People with ST-segment
elevation are faced with a high risk of going through coronary angiography, which is
important when it comes to diagnosis of TCM (Madhavan et al., 2009). Although, these ECG
characteristics help in diagnosing TCM and ACS,no ECG criteria have been identified that
reliably discriminate between TCM and STEMI(Scantlebury and Prasad, 2014).
Furthermore,imaging studies and other measures are needed to rule out ACS to get a
definitive diagnosis. The ability of medical practitioners, in distinguishing these
characteristics, will assist medical professionals not to fall into the trap of misdiagnosing the
condition.
Even though initial ECG in patients that have TCM is usually nonspecific, it is
possible that ST segment elevation can be found in pre cordial lead in 50% of patients, at

7. TCM in ASC Diagnosis 7
initial onset(Scantlebury and Prasad, 2014). Additionally, it is understood that one is unlikely
to find reciprocal ST segment depression in the inferior wall (Haghi et al., 2010). Taking into
consideration comparison with patients who have other deformities, inverted T waves can be
observed more often in patients who show signs of an apex dilation that is balloon like.
Furthermore, patients with TCM also show abnormal forms of Q waves that are usually
transient in most patients and can be resolved within a short period of time which can be a
day, or in some cases, several days. However, in patients with myocardial infarction, a
pathologic Q wave is frequently unresolved. When it comes to patients with chest pain that
suggests a possibility of ACS, it is recommended practice that they are put through a process
of 12-lead ECG. After a period of ten minutes, they must be evaluated in order to detect any
ischemic changes (Krishnamoorthy et al., 2015). In any case where the ECG that has been
performed is not correctly indicative of what the patient could be suffering, yet the medical
practitioner has a high suspicion that ACS might be the main problem, a series of ECGs must
be carried out at 15 minutes intervals in the first hour, with the main aim of determining any
forms of ischemic changes. Therefore, regular ECGs are significant as distinctive changes
have now been defined and the potential for deterioration of the QT interval is important in
risk stratification and may assist in distinguishing TCM from ACS.Although, no evidence is
reported that QT interval calculation can help diagnose accurately at presentation.
The medical understanding is that inverted T waves in most cases appear in patients
with ACS, but can also be noted in patients with TCM. It is possible to determine the
difference in diagnosis of ACS and TCM due to significant differences in inverted T waves.T
wave’s inversion in precordial leads can suggest severe ischemia under the left ventricular
wall; this can be attributed to critical stenosis of the LAD (Hoyt et al., 2010). Yet such
observations have also been determined under the TCM which has new electrocardiographic
anomalies. Different diagnosis is essential to differentiate TCM from ACS. This ensures that

8. TCM in ASC Diagnosis 8
the form of treatment is appropriate and directed towards positive outcomes (Prasad et al.,
2014). To determine the difference between TCM and ACS, one has to study admission
ECGs in some patients. The patients must be observed in the care facility within 48 hours
from the onset of symptom and if they have had inverted T waves equal to or greater than 1
mm (Summers et al., 2010). When such investigation is carried out, it is possible to determine
that, maximal amplitude and numbers of the inverted T waves were more in patients with
TCM. The patients with ACS had a lower number as well as maximal amplitude. The
electrocardiographic changes that occur in TCM have indicated their similarities to those
found in the anterior AMI (acute myocardial infarction) (Singh et al., 2014). This is different
to that which takes place in patients with ACS, where non STEMI patients have more
commonT waves than ST segment changes. The inverted T waves are usually followed by ST
segment elevation which in most cases exists in leads that face the site of myocardial
ischemia. The artery connected to the ischemia and the perfusion territory can be determined
through following the distribution of the inverted T waves. In patients who have TCM and
ACS, inverted T waves can occur without ST-segment elevation at a presentation of ECG,
when one focuses on the T waves changes in leads III, aVR and V1 can lead to differentiation
between ACS and TCM. However, ECG criteria alone are inadequate to differentiate ACS
syndrome from TCM.
In general, during presentations, the biomarkers of cardiac myonecrosis are usually
elevated in more than 90% of TCM cases (Pilgrim and Wyss, 2008). Usually, the biomarker
levels, in most of the cases, go high within 24 hours after their presentation, yet the levels are
usually lower than that which would be anticipated on the basis of abnormalities on wall
motion, as well as findings in the electrocardiogram (Parkkonen et al.,2014). However, there
are various cases in which the level of biomarkers is significantly raised in the absence of
myocardial damage. When troponin levels are measured and found to be elevated in any

9. TCM in ASC Diagnosis 9
individuals suspected to have ACS, it is important to eliminate other causes that could lead to
raised troponin. Examples include aortic dissection, pulmonary embolism, myocarditis, renal
failure and TCM that leads to avoidable unnecessary cardiac testing. This must be done
before the patient is diagnosed with ACS (Kumar et al., 2010). It is always important to
follow the correct guidance provided by NICE when a patient shows signs of high troponin
levels, until the most accurate and firm diagnosis is reached. The levels of cardiac-specific
troponin are usually measured at the point of presentation or 3 to 6 hours from the onset of
the symptoms in patients who show high signs of ACS. This is done to monitor if there are
marked elevations of troponin levels which clearly distinguishes TCM from ACS, however,
there are no specified levels used as a cut off measurement biomarkers in distinguishing ACS
from TCM. In cases of patients with normal troponin levels six hours after admission,
additional readings of troponin levels should be gathered beyond the six hours (Deshmukh,
2016). There are cases when the time of symptom is difficult to determine. Hence, it is
recommended that the time of presentation should be used as the time of onset, when
assessing the value of troponin. Cardiac biomarkers are important when it comes to
prognosis. The troponin is determined in two aspects; the magnitude and the presence, both
which are very important in the short and long term prognosis of the syndrome. It is advisable
that one should engage in the remeasuring process, on the third or even fourth day. This is
done on patients with ACS, as dynamics of necrosis, or as an index of the infarct (Dib et al.,
2009). Noticeably,a rapid but small rise in cardiac biomarkers is noted on patients with TCM
syndrome, while cardiac biomarkers in patients with STEMI take longer to rise but peak
higher. Therefore, troponin levels and prevalence over time can be used to differentiate ACS
from TCM

10. TCM in ASC Diagnosis 10
The most recent case study, carried out on 97 patients from Japan with TCM, showed
a 10% incidence of coronary artery disease (Kurisu et al., 2009). There was another case
study, which described seven patients who had presentations consistent with TCM and had
epicardial coronary artery or more than 70% of stenosis (Citro et al., 2013). There are several
areas within which imaging options are possible and they range from angiography wherein
coronary anatomy can be evaluated and cardiac magnetic resonance, under which, an
assessment of tissue characterization can be carried out. Percutaneous Coronary Intervention
(PCI) is an important element which is used to improve outcome in patients who have acute
ST elevation. In carrying out the task highlighted above, there are certain technical and
adjunctive medications that are important during the periprocedural period. It is important to
understand that PCI is a non-surgical technique that can be applied when treating any form of
obstructive coronary artery disease or infarction (Dundon et al., 2009). To determine the
nature of the disease that is suffered, one has to look at the indications, as well as
contraindications for PCI. Should a patient show any signs of STEMI, an immediate
angiography with PCI must be carriedas a therapeutic management. However, in TCM
patients this is used to assess the wall motion abnormalities as this may improve in hours and
maybe missed if coronary imaging is delayed resulting to misdiagnosis and mismanagement
of the syndrome (Haghi et al.,2010). Coronaryangiography can be considered if the procedure
can be performed within the recommended door to balloon guidelines. Furthermore, such
procedure must not be applied at the expense of delaying lifesaving reperfusion therapy from
patients with STEMI if the patient is assessed and diagnosed where coronary angiography is
not available.
Conclusion
Thus, despite similarities in symptoms, ASC and TCM are two very distinct ailments
with different causes and different implications for patients’ health. The onset of both

11. TCM in ASC Diagnosis 11
syndromes is preceded by chest pains, a factor that has increased the chances of misdiagnosis
especially that of TCM as ACS, mostly in patients who have inverted T waves under the first
ECG.This has the potential of leading to inappropriate treatment, as well as presentation.
However, initial tests of troponin levels in patient blood samples may be used to determine
whether a patient has suffered from ASC or TCM. In ASC, there is either total or partial
damage of tissues within the heart, which leads to the release of troponin, leading to
increased levels of the latter in the blood in ASC patients as compared to TCM patients.
There are lower levels of troponin among TCM patients as there is no actual damage to heart
tissues, as the ailment involves mainly an inflation and ballooning of specific parts of the
right ventricle. However, ECG changes and troponin level measures alone are not sufficient
to differentiate TCM syndrome from ACS. It is, therefore, important to note that diagnosing
TCM demands coronary angiography, continuous assessment of left ventricle systolic
functionality (through initial general evaluation by echocardiography or ventriculography
followed by an overall assessment by echocardiography) and electrocardiogram. Identifying
the difference between the two syndromes is important as different treatment or management
is provided for each of them.In selecting treatment for patients at greater risk of
complications, risk stratifications are to be considered. It is worth noting that TCM is less life
threatening, often taking about a day to heal, compared to ASC which in many cases is fatal.
This makes it necessary for further study into the differences between the two syndromes to
enable early detection and reduce misdiagnosis of either of them as the results could be fatal.

12. TCM in ASC Diagnosis 12
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