Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Stress-Induced Cardiomyopathy: A Case of Takotsubo

Cardiomyopathy and Review of Literature
Christian Camilo Lasso Maldonado*, Sebastián Salvador Barrera Beltrán*, Jorge Arturo Lozada Hernández*
*Universidad del Rosario - Escuela de Medicina y Ciencias de la Salud – Fundación Santa Fe de Bogotá
Bogotá D.C. – Colombia

Abstract:- Takotsubo syndrome is an acute cardiomyopathy characteristic alterations in myocardial contractility of the left
with a clinical presentation similar to acute coronary ventricle, generally reversible [2]. The etiology of this
syndrome, characterized by reversible alterations in syndrome is not completely defined; it has been associated with
ventricular function, leading to complications of acute heart an exaggerated discharge of sympathetic activity
failure in the absence of underlying coronary artery disease. (catecholamine cardiotoxicity), leading to coronary spasm and
Its triggering pathophysiology is unknown and there is no microvascular dysfunction [4]. It has typically been considered
consensus regarding its treatment. A clinical case of unusual a benign pathology; its management is based on the control of
characteristics is presented, which debuted in peripheral sympathetic activity with beta-blockers [16].
cardiorespiratory arrest secondary to polymorphic
ventricular tachycardia, with rapid return to spontaneous II. CASE PRESENTATION
circulation, and good response to medical management.
A 66-year-old female patient with a history of
Keywords:- Takotsubo, Broken Heart Syndrome, Stress-Induced dyslipidemia under management with atorvastatin and
Cardiomyopathy, Cardiomyopathy. apparently episodes of nonsustained ventricular tachycardia for
30 years that is not being managed at the moment, with no other
I. INTRODUCCIÓN cardiovascular risk factors, who comes to the emergency
department for an episode of oppressive chest pain of
Takotsubo syndrome is an acute cardiomyopathy with a approximately 30 minutes duration, which occurs during the
clinical presentation similar to acute coronary syndrome [1]. funeral of her sister. The patient was admitted to the emergency
This heart disease was first described in Japan in the 1990s [2]. department for an episode of oppressive chest pain lasting
it is a rare condition, accounting for approximately 1% of all approximately 30 minutes, which occurred during her sister's
patients with chest pain and suspected acute coronary syndrome funeral. On admission to our institution, she presented
[3]. it mainly affects postmenopausal women, with an cardiovascular collapse with witnessed cardiorespiratory arrest,
associated episode of severe emotional or physical stress. Its arrest rhythm monomorphic ventricular fibrillation, high
presentation as chest pain with anginal features, quality resuscitation was initiated and defibrillation with 200J
electrocardiographic changes and elevation of cardiac enzymes was administered on 2 occasions, and she returned to
make early diagnosis difficult [1,3], until the absence of spontaneous circulation with resuscitation maneuvers.
coronary obstruction is found on angiography and the

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Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165

Fig 1: Angiographic evaluation A. Left Circulation B. Right Circulation

 Coronary arteries without evidence of occlusion  End diastole

The post-resuscitation electrocardiogram shows  Isovolumetric contraction
alterations in the ST segment and J point given by low level in  End systole
anterior and lateral face, associated with positive cardiac
enzymes (troponin i (HS): 42.9ng / l range: 0.0 - 11. 6), is During his stay in the Intensive Care Unit, complete
immediately taken to coronary angiography, ruling out anticoagulation was started with low molecular weight heparin
angiographically significant coronary artery lesions (Figure 1); (1mg/kg/BID), statins in intensive doses, angiotensin
Transthoracic echocardiogram shows severe compromise of converting enzyme inhibitor + beta-blocker in low doses
systolic function, with severely decreased ejection fraction (enalapril 2.5mg/BID + metoprolol 12.5 mg/day). However,
(LVEF: 26%), also with alteration in segmental contractility with the onset of hemodynamic instability, ACE inhibitors and
given by akinesia of the middle and distal segment of the beta-blockers were suspended, requiring vasopressor support
interventricular septum, akinesia of the middle and distal with low-dose noradrenaline and inotropy with levosimendan;
segment of the inferior, posterior, lateral and distal segment of with early withdrawal less than 24 hours later, also meeting
the anterior wall with left ventricular ballooning, findings clinical and gasometric criteria for controlled awakening, with
suggestive of Takotsubo's heart disease (Figure 2). adequate tolerance to weaning from mechanical ventilation, so
she was extubated early. She was considered a candidate for
implanted cardiodesfibrillator, as a strategy for secondary
prevention of sudden death; with good evolution and adequate
clinical status, she was discharged after four days.

Stress cardiomyopathy, also called takotsubo

cardiomyopathy/syndrome, apical balloon syndrome or broken
heart syndrome, is a syndrome characterized by transient and
reversible regional systolic dysfunction, mainly affecting the
apical area of the left ventricle, causing the ventricle to dilate,
leading to transient and completely reversible heart failure in
most cases (<21 days). This contractile compromise, which is
not explained by an ischemic lesion, as it characteristically
Fig 2: Echocardiographic evaluation of ventricular function on affects more than one coronary vascular territory (epicardial
admission transthoracic echocardiogram (apical 4-chamber coronary arteries) [1,2], was first described by Hikaru Sato in
window) shows evidence of left ventricular ballooning. 1990 in Japan, with the name "takotsubo" comes from the

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Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Japanese term for an octopus fishing trap, which has a shape Catecholamines released in large quantities
similar to the apical systolic balloon of the dilated left ventricle, (catecholamine toxicity) induced by physical or emotional
which is the most frequent and typical form of presentation of stress can cause diffuse and transient microvascular spasm
this disorder [5]. It accounts for 1 - 2% of patients with chest directly compromising coronary flow [1,8], in addition to
pain [1,4,6], affects mainly women, with an approximate generating direct cardiotoxicity on cardiomyocytes. Excess
female: male ratio of 9:1, usually postmenopausal women catecholamines induce intracellular calcium overload,
between 55 and 65 years of age, and in up to 70% of cases a inhibiting the expression of SERCA2a (sarcoplasmic-Ca2+-
stressful event (physical or emotional) is identified [2,3]. adenosinetriphosphatase), which generates a rapid increase in
the phospholambam/SERCA2a ratio, causing a decrease in
Takotsubo cardiomyopathy is classified into four main calcium affinity and resulting in alterations of myocardial
variants according to the anatomical distribution of the contractility, reaching a state similar to post-ischemic
contractility alterations: apical, basal, mid-ventricular and focal myocardial stunning [1,5,6] [1,5,6].
[7,8,9].
IV. DIAGNOSIS
 Apical type: This is the classic form that represents 80% of
cases, characterized by basal hyperkinesia, apical The clinical picture is similar to that of an acute coronary
ballooning and hypokinesia of the apical segments, which syndrome, the cardinal symptom is usually chest pain with
may extend to the midventricular segments. It is associated anginal features, preceded by an episode of intense emotional
with further complications, mainly mechanical, such as left or physical stress, which is identified in more than 70% of
ventricular outflow tract (LVOT) obstruction and mitral patients [1,2] . In a systematic review of 19 studies and 1109 of
valve insufficiency [8,10]. 2015 Pelliccia F., et al, found that in approximately 13% of
 Basal type: Characterized by basal hypokinesia and apical patients it is not possible to determine the triggering event [3],
hypercontractility, it has been found to be associated with and that patients with psychiatric or neurological disorders,
subarachnoid hemorrhage and pheochromocytoma [11]. mainly intracranial hemorrhage, are more predisposed to
 Midventricular type: characterized by hyperkinesia of the develop stress cardiomyopathy [2,3].
apical segment and dyskinesia of the bulging midventricular
region, giving a hawk beak appearance on the left The most common presenting symptom is chest pain, but
ventriculogram, this variant was first described by Roncalli it may present with other anginal equivalents such as dyspnea
et al. in 2007 [8,12,13]. or syncope [1,10], Pelliccia F., et al, found that more than half
 Focal type: characterized by isolated dysfunction of the of the patients presented chest pain as the cardinal/initial
anterolateral segment of the left ventricle [8]. symptom (55%), followed by dyspnea (26%), as well as more
than half of the patients presented ST alterations (53%) mainly
in the anterior leads [3], other less frequent electrocardiographic
alterations have also been described, such as QT interval
prolongation, T wave inversion, ventricular tachycardia (VT),
ventricular fibrillation (VF) and torsade de pointes [2]. Gili S,
et al, performed a subgroup analysis of the InterTAK Registry,
finding that of the 2098 patients, 84 presented as cardiac arrest,
of which 44% were found as ventricular fibrillation in arrest
rhythm (37 cases), 42, 9% pulseless electrical activity (36
cases) and ventricular tachycardia in only 13.1% of cases (11
Fig 3: Graphical representation Anatomical Variants patients) [11,14], these life-threatening arrhythmias occur early
in patients with Takotsubo syndrome (first 24 hours), are
The apical variant is considered as the typical Takotsubo associated with a significant worsening prognosis in the short
syndrome, and the basal, midventricular and focal variants as and long term. Jesel, et al. in a cohort of 214 patients collected
atypical forms, mainly related to young patients, less over 8 years, identified decreased left ventricular ejection
compromised ejection fraction, electrocardiographic changes fraction (LVEF) and conduction disturbances (QRS >105ms) as
mainly ST depression and lower mortality [8,9], however, there independent predictors for the development of life-threatening
seems to be no difference in terms of short and long-term arrhythmias, with a significant increase in both factors. in-
mortality between the different anatomical patterns [9]. hospital and 1-year mortality (39.1 % vs 8.9 %; P < 0.001 and
47.8 % vs 14.1 %; P < 0.001 respectively) [12].
III. PATHOPHYSIOLOGY
these life-threatening arrhythmias occur early in patients
The causal mechanism is not clearly defined; it has been with Takotsubo syndrome (first 24 hours), are associated with a
associated with catecholamine excess (catecholamine toxicity), significantly worse short- and long-term prognosis. Jesel, et al.
microvascular dysfunction, and coronary spasm [2]. in a cohort of 214 patients collected over 8 years, identified
decreased left ventricular ejection fraction (LVEF) and

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Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
conduction disturbances (QRS >105ms) as independent
predictors for the development of life-threatening arrhythmias, Table 2: InterTAK Diagnostic Score [15]
with a significant increase in both factors. in-hospital and 1-year Criteria Points
mortality (39.1 % vs. 8.9 %; P < 0.001 and 47.8 % vs. 14.1 %;
P < 0.001 respectively) [12]. Female Sex 25

Elevation of troponin is also characteristic, as are other Emotional Trigger 24

markers of myocardial injury such as natriuretic peptides (BNP
Physical Trigger 13
and Pro-BNP) (Table 1) [1,3]; Wittstein et al. found that plasma
levels of catecholamines were two to three times higher in Absence of ST-segment Depression 12
patients with Takotsubo cardiomyopathy than in patients with
myocardial infarction [4,10]. Psychiatric Disorders 11

Table 1: Biomarkers in Takotsubo syndrome Neurologic Disorders 9

QTc Prolongation 6
Biomarker Troponin BNP NT-
proBNP 100
Clinical predictors takotsubo syndrome
Takotsubo ↑ ↑↑ ↑↑ *Absence of ST-segment depression, Except in lead aVR
Cardiomyopathy
Acute Myocardial ↑↑ ↑ ↑ However, significant coronary artery disease may coexist
Infarction in a high proportion in patients with stress cardiomyopathy,
Napp LC, et al in a study that collected a total of 1016 patients
with Takotsubo syndrome, defined according to the InterTAK
Diagnostic Criteria, found that 23.0 % had concomitant
The diagnosis of this entity is to rule out an acute coronary coronary artery disease with significant obstruction, of which
syndrome of the myocardial infarction type, for which the Mayo 47 patients required percutaneous coronary intervention, an
Clinic Diagnostic Criteria were proposed to facilitate the additional 41.2% had non-obstructive coronary artery disease
approach [3,7,14]. and only 35.7% had angiographically normal coronary arteries
[6], so the diagnosis of stress cardiomyopathy requires serial
 Transient left ventricular dysfunction: temporary evaluation of ventricular systolic function to define the
hypokinesia, dyskinesia or akinesia in LV segments with or reversibility of the changes presented.
without apical involvement, involving more than a single
vascular distribution. V. TREATMENT
 Absence of significant obstructive coronary artery disease
on arteriography. It has been considered a benign pathology, so treatment is
 Recent changes detected on electrocardiogram (ECG) (ST- generally conservative, with supportive therapy, seeking to treat
segment elevation and/or T-wave inversion) or significant symptoms, resolve physical or emotional stress, prevent the
elevation of serum cardiac troponins. development of complications and reduce recurrence. However,
 Absence of pheochromocytoma or myocarditis. no guidelines have been established for its management and
therapeutic strategies are based on clinical experience and
The InterTAK Diagnostic Scale, is a score composed of 7 expert consensus.
variables (Table 2) all parameters are easily obtained in the
emergency department and no diagnostic imaging is needed to  Beta-blockers
complete it, which estimates the probability of presenting Beta-blockers such as carvedilol [14,16] have been
Takotsubo syndrome, to try to differentiate it from acute proposed to control the myocardial response to catecholamine
coronary syndrome, its main differential diagnosis. In 2016 excess and also to reduce the incidence of arrhythmias;
Jelena R, et al validated the score with a derivation cohort However, their use should be cautious, since their use is
(Takotsubo, n = 218; acute coronary syndrome, n = 436), contraindicated in patients with suspected coronary spasm, very
recruited from the International Takotsubo Registry low LVEF, hypotension, bradycardia or QTc > 500 ms, because
(www.takotsubo-registry.com) and from a leading hospital in of the possibility of worsening LVOT and leading to
Zurich [15]. An optimal value for the diagnosis of Takotsubo cardiogenic shock, so they should be started with caution and
syndrome of ≥70 points was established, with a sensitivity of gradually increased according to clinical response [17]. It is not
89 % and a specificity of 91 %; with an area under the curve possible to give a clear recommendation on the use of beta-
(AUC) of 0.971 [95 % confidence interval (CI): 0.96-0.98] [15]. blockers; trials are needed to support this hypothesis.

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Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Angiotensin-converting enzyme inhibitors (ACEi) or electrical therapy, the early presence of a malignant arrhythmia
angiotensin II receptor blockers (ARB-II). that led to cardiorespiratory arrest is unusual, El-Battrawy et al.
Segmental contractility disorders usually resolve found that more than half of the patients with Takotsubo
spontaneously, ACEi/AR-II have been proposed to counteract syndrome who presented arrhythmias presented cardiac arrest
persistent activation of the renin-angiotensin-aldosterone [13].
system, decreasing afterload, limiting cardiac remodeling and
limiting recurrence [10,16,17]. The electrocardiographic findings in the acute phase,
mainly persistent ST-segment inversion in the inferior aspect of
The most frequent complication of Takotsubo the heart, associated with troponin elevation, suggested a
cardiomyopathy is acute heart failure and cardiogenic shock, coronary occlusive compromise, which was ruled out by
which occurs in approximately 20% of patients. In general, coronary angiography. In addition, the patient's
management is according to standard guidelines for heart echocardiography showed akinesia of the middle and distal
failure with reduced ejection fraction (HFrEF), controlling segment of all left ventricular walls, with apical ventricular
preload and reducing afterload [8], careful water resuscitation ballooning, configuring a typical Takotsubo syndrome; which
should be initiated, early initiation of non-adrenergic inotropic is not concordant with InterTak score of 49 points (woman +
drugs such as levosimendan should be started. considered emotional stress), the patient had an intermediate/low
[18,19], limiting the use of beta-blockers [14,18]. probability of presenting this syndrome.

Left ventricular outflow tract (LVOT) obstruction occurs The presence of ventricular arrhythmias in patients with
when the base of the heart contracts forcefully, making blood Takotsubo syndrome represents a negative prognostic factor
flow in the aortic outflow tract very turbulent, causing mitral that increases in-hospital morbidity and the risk of sudden
insufficiency due to involvement mainly of the anterior leaflet. cardiac death [20], there is no clear recommendation regarding
This phenomenon occurs in approximately 10% of patients, the treatment of electrical complications in patients with
most frequently in the classic (apical) variant of Takotsubo Takotsubo syndrome, since it is considered a reversible
cardiomyopathy [20]. pathology, ideally drugs that prolong QTc should be avoided,
since it has been documented that a corrected QT interval >500
Early recognition of OTVI is important, as these patients ms or a QRS >105ms [12,20], are an arrhythmogenic risk factor
respond differently to treatments [20]: for developing ventricular tachycardia; in our patient neither of
 afterload reduction and diuretics may worsen OVTI these 2 characteristics was documented during observation. In
 Inotropic agents may exacerbate OVTI. addition, strict monitoring of beta-blockers and renin-
angiotensin-aldosterone system inhibitors is necessary to avoid
VI. PROGNOSIS bradycardia and hypotension [16,18].

In general, the prognosis of Takotsubo cardiomyopathy is The implantation of permanent electrical devices in
good. About 95 % of patients fully recover LV function, may patients with Takotsubo syndrome is a controversial issue,
begin to recover within several days, and recover completely without finding a clear recommendation in ventricular
within 3 to 4 weeks [8], seems to depend, at least in part, on the arrhythmias, in general, the possibility of recurrence should be
triggering factor. considered as the determining factor for the implantation of
these devices. In the case presented, the debut with
Patients with Takotsubo syndrome are at high risk for monomorphic ventricular tachycardia leading to cardiac arrest,
cerebrovascular events mainly during the first 30 days, so it is the severity of the arrhythmia, the good functionality and high
preferred to initiate prophylactic anticoagulation in high-risk life expectancy of the patient led the treating group to consider
patients, such as the presence of a large area of myocardial implanting a cardio defibrillator.
hypokinesia mainly with apical involvement [8].
VIII. CONCLUSIONS
VII. DISCUSSION
Takotsubo syndrome is a transient and reversible
The reported case presented clinical features that are cardiomyopathy, generally with a good prognosis. It is
considered atypical in Takotsubo syndrome. The characterized by apical ballooning of the left ventricle,
electrocardiographic, kinetic and myocardial conduction associated with a recent episode of physical or psychological
alterations found in the patient of the case represent a low stress, which is not identifiable in all cases. Catecholamine
incidence in the literature reports, and its rapid temporal levels have been shown to play a vital role in the pathogenesis
evolution led to a near-fatal complication. the debut of the and pathophysiology, inducing diffuse vasospasm and
pathology that led to cardiorespiratory arrest was of rapid microvascular dysfunction secondary to the adrenergic storm
evolution, with approximately 30 minutes of symptomatology generated. Due to its clinical features, EKG changes and
prior to admission to the emergency department, with a more increased cardiac biomarkers, its presentation is very similar to
than favorable response to resuscitation maneuvers and acute myocardial infarction, so this should be its main

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Volume 9, Issue 1, January – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
differential diagnosis and a careful diagnostic approach should [10]. Randhawa MS, Dhillon AS, Taylor HC, Sun Z, Desai MY.
be performed, characteristically finding healthy coronary Diagnostic utility of cardiac biomarkers in discriminating
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