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Abstract
Takotsubo Syndrome (TS) is a transient cardiac condition

characterized by regional systolic dysfunction, often precipitated
by emotional or physical stressors. The pathophysiology of TS is
not fully understood, but evidence suggests that it may be influ-

enced by multiple factors. We present a case of TS following a
traumatic left humerus fracture in an 82-year-old male patient with
hypertension. Diagnosis was confirmed through comprehensive
clinical evaluation, identification of ECG abnormalities, echocar-
diographic findings, and exclusion of other diseases. The patient’s
management consisted of β-blockers, aspirin, and supportive care.
Despite initial concerns, the patient’s clinical course was unevent-
ful, illustrating the various presentations of TS. This case empha-
sizes that TS can occur as a result of a traumatic event, particularly
among older individuals with comorbidities. Early recognition and
appropriate management are essential for optimizing outcomes.

Introduction
Transient Left Ventricle (LV) apical ballooning, also referred

to as Takotsubo Syndrome (TS), is characterized by short-lived
(usually lasting 24 to 48 hours) regional systolic dysfunction,
dilatation, and oedema involving the LV apex and/or midventricu-
lar region in the absence of coronary artery disease.1,2 The patho-
physiology of TS is not fully understood, but evidence suggests
that it may be influenced by various factors (i.e., acute multivessel
coronary spasm, aborted myocardial infarction with spontaneous
recanalization, and direct catecholamine-mediated myocardial
stunning).3 A preceding emotional or physical stressor is a typical
feature of TS; indeed, physical, emotional, or mixed stressful
events have been identified in two-thirds of takotsubo cardiomy-
opathy cases (such as acute critical illness, trauma, respiratory fail-
ure, central nervous system disorders, and iatrogenic factors
including surgery or dobutamine stress echocardiography).1 The
incidence of TS has been reported to be between 5.7% and 28.0%
in intensive care units.4 Post-traumatic TS has been reported main-
ly in brain injury, chest, and lower limbs. Accidental falls and road
accidents are the main causes of injuries [4]. Herein, we describe
the case of a patient admitted to the Emergency Department for a
left humerus fracture who developed trauma-related TS.

Case Report
An 82-year-old male patient was admitted to the Emergency

Department because of an accidental fall from a height of 1.5
meters, resulting in trauma to the left shoulder. The patient report-
ed no loss of consciousness, chest pain, or dyspnea, and denied any
head trauma or other injuries. His medical history disclosed arterial
hypertension, for which he was treated with an Angiotensin
Receptor Blocker (ARB). Physical examination revealed moderate
left shoulder pain (NRS=6) with overt dislocation localized defor-
mity, while neurological and thoraco-abdominal examinations
were unremarkable. Vital signs were within normal limits.
Computed Tomography (CT) of the head showed no abnormalities,
while X-ray of the left shoulder revealed a displaced multi-frag-
mentary fracture of the huemerus. The Electrocardiogram (ECG)

                                              Emergency Care Journal 2024; volume 20:12647

                                                                         [Emergency Care Journal 2024; 20:12647]                                                      [page 113]

A left humerus fracture-induced Takotsubo syndrome
Alessandro Rapino,1 Giovanna Ceccuzzi,1 Benedetta Perna,1 Giacomo Maroncelli,1 Michele Domenico Spampinato,1,2

Gabriele Farina,3 Roberto De Giorgio,1 Matteo Guarino1,2

1Department of Translational Medicine, St. Anna University Hospital of Ferrara, University of Ferrara; 2Emergency Department, 
S. Anna University Hospital of Ferrara; 3Emergency Department, AUSL Romagna, Faenza Hospital, Ravenna, Italy

Correspondence: Roberto De Giorgio, Department of Translational
Medicine, St. Anna University Hospital, via A. Moro 8, 44124 –
Ferrara, Italy
Tel.: +39.0532.236631
E-mail: dgrrrt@unife.it

Key words: emergency medicine; fracture; humerus; Takotsubo car-
diomiopathy; trauma.

Contributions: AR, GC, GM, and MG designed the project and
wrote the paper. AR, GC, and BP searched the literature for retriev-
able papers. MDS, GF, RDG, and MG critically reviewed the paper.
All authors have read and agreed to the published version of the
manuscript.

Ethics approval and consent to participate: no ethical committee
approval was required for this case report by the Department,
because this article does not contain any studies with human partic-
ipants or animals. Informed consent was obtained from the patient
included in this study.

Patient consent for publication: the patient gave his written consent
to use his personal data for the publication of this case report and any
accompanying images.

Availability of data and materials: all data underlying the findings
are fully available.

Funding: RDG is supported by ‘Fondi Ateneo per la Ricerca’ (FAR)
and ‘Fondi Incentivazione alla Ricerca’ (FIR) research funds from
the University of Ferrara, Ferrara, Italy.

Received: 8 May 2024.
Accepted: 24 July 2024.
Early view: 29 July 2024.

This work is licensed under a Creative Commons Attribution 4.0
License (by-nc 4.0).

©Copyright: the Author(s), 2024
Licensee PAGEPress, Italy
Emergency Care Journal 2024; 20:12647
doi:10.4081/ecj.2024.12647

Publisher's note: all claims expressed in this article are solely those of
the authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article or claim that may be
made by its manufacturer is not guaranteed or endorsed by the publisher.

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showed slight T-wave inversion in V4-V5 (Figure 1, panel A), with
no previous ECGs available for comparison. After three hours, the
ECG showed deepening of T waves (Figure 1, panel B). A con-
trast-enhanced CT of the chest and abdomen ruled out post-trau-
matic effusions. Blood tests revealed elevated troponin levels,
hypokalemia, and hypocalcemia (Table 1). Transthoracic echocar-
diography (Figure 2A, B and C) showed no pericardial effusion,
good contractility of the basal portions of the heart, slightly hypo-
mobile apex, and an inferior vena cava of approximately 2 cm in
caliber with poor respiratory excursions, a finding indicative of
central venous pressure >8 mmHg. Coronary angiography was per-
formed to exclude mechanical obstruction (Figure 2D). The patient
met the Mayo Clinic diagnostic criteria with positive troponin
delta, ECG abnormalities, apical ballooning on echocardiography,
negative coronary angiography, and exclusion of other diseases.5

Because of this clinical picture, the patient was prescribed β-block-
ers, aspirin, and low molecular weight heparin, in addition to a
combination of paracetamol and codeine for pain control. During
hospitalization, ECG showed QT prolongation, which progressive-
ly normalized at discharge, along with troponin levels. Based on
orthopedic consultation, the upper limb was immobilized with a
collar and cuff sling, and non-operative management of the frac-
ture was deemed the right therapeutic option based on the patient’s
age and co-morbidities. The patient was discharged after 11 days
in good conditions with a diagnosis of “Takotsubo syndrome asso-
ciated to a fracture of the left humerus”.

Three months later, a follow-up echocardiography showed no
cardiac kinetic abnormalities, hence β-blockers were discontinued,
while aspirin was maintained.

                             Case Report                                                                         

Table 1. Synopsis of the main laboratory features and troponin profile over time of the reported patient.

Feature                                                  Values on admission to the emergency department               3h                    6h                         12h

WBCs (x10^3/μl) (4.0<n.v.<11.0)                9.19
RBCs (x10^6/μl) (4.5<n.v.<6.5)                   4.31
HGB (g/dl) (13.0<n.v.<18.0)                         13.5
Plts (x10^3/μl) (150<n.v.<450)                     214
INR (0.80<n.v.<1.20)                                    0.97
Creatinine (mg/dl) (0.50<n.v.<1.20)             0.95
Sodium (mmol/L) (136<n.v.<145)                141
Potassium (mmol/L) (3.5<n.v.<5.3)              3.0
Calcium (mg/dl) (8.6<n.v.<10.2)                  7.0                                                                                                               
Troponine (ng/L) (n.v.<15)                            71                                                                                                                253                     328                           198
HGB, Haemoglobin; INR, International Normalized Ratio; Plts,  Platelets; RBC,  Red blood cell; WBC, White blood cell.

[page 114]                                                           [Emergency Care Journal 2024; 20:12647]

Figure 1. Patient’s electrocardiogram (ECG) on admission to (A)
and after 3 hours in (B) the Emergency Department.

Figure 2. Echocardiographic (A, B and C) and coronographic
images (D) of the present case showing the typical left ventricular
apical ballooning.Non

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Discussion
Originally reported in Japan in 1990, TS and its variants is

defined as an acute and reversible cardiac failure.1 The Mayo
Clinic criteria are widely used for diagnosis and include: i) the
presence of transient hypokinesis, akinesia / dyskinesia of the left
ventricular mid-segments with or without apical involvement;
regional wall motion abnormalities that extend beyond a single
epicardial vascular distribution; and (frequently) a stressful trigger;
ii) the absence of obstructive coronary disease or angiographic evi-
dence of acute plaque rupture; iii) new ECG abnormalities and/or
modest elevation in cardiac troponin; and iv) the absence of
pheochromocytoma and myocarditis.4-6

TS can be classified as primary or secondary. In primary
forms, acute cardiac symptoms are the main reason for seeking
medical attention. Conversely, secondary TS is recognized in
patients who are already hospitalized for a medical or surgical con-
dition (e.g., acute respiratory failure, traumatic injury, sepsis),2,3 as
in the present case. Furthermore, primary and secondary TS
include different anatomical variants. A typical variant, found in
about 50-70% of patients, including our patient, is characterized by
left ventricular regional wall motion abnormality with apical and
circumferential mid-ventricular hypokinesia.2,7 At end-systole, the
left ventricle resembles the ‘Takotsubo’ (the Japanese fishing pot
used for trapping octopus) with a narrow neck and globular lower
portion.2 The other two common phenotypes include the basal or
inverted variant with circumferential basal hypokinesia8 and the
mid-left-ventricular variant, with circumferential mid-ventricular
hypokinesia and both basal and apical hypercontractility.9 Rare
variants encompass biventricular apical dysfunction and isolated
right ventricular TS.2

The exact pathophysiological mechanism of TS remains
unclear, but it might include coronary vasospasm, microcirculatory
dysfunction, catecholamine surge, and sympathetic overdrive.2
Excessive levels of catecholamines released by the sympathetic
nervous system could result in intracellular calcium overload and
cardiac dysfunction through the β1-adrenoreceptor signal trans-
duction pathway. Moreover, patients with TS also consistently
demonstrate microvascular dysfunction features, i.e. impairment
of endothelium-dependent vasodilation, excessive vasoconstric-
tion, and abnormalities of myocardial perfusion.6

The incidence of TS is estimated to be around 2% of all acute
coronary syndromes.10 In most cases, TS occurs in female and
post-menopausal patients due to emotional stressful triggers,6,11

while it is rarely observed in male patients and is generally induced
by physical stress (i.e., activity/trauma, infections, hypoxia, neuro-
logical disorders, surgery, pain).12 To our knowledge, male patients
who develop TS are usually younger (69±13 vs. 71±11 years) and
with higher prevalence of comorbidities (i.e., hypertension, dia-
betes, pulmonary disease, malignancies, and smoking habit) than
females.12 In male patients TS manifests with chest pain, dyspnoea
and palpitations with sinus tachycardia; in severe cases, pre-syn-
cope and syncope due to ventricular tachycardia and Major
Adverse Cardiovascular Events (MACEs) may occur.2 However,
chest pain is not a frequent initial complaint in males; indeed, in a
few cases, the main concern was the ECG findings, as in our case.
Although no pathognomonic ECG findings have been described,
reversible abnormalities like ST-segment elevation in the anterior
leads (56%) and T-wave inversion (39%)13 are common. Less fre-
quently, QT prolongation and malignant arrhythmias (i.e., ventric-
ular tachycardia, ventricular fibrillation, and torsade de pointes)
might occur. As shown in the present case, the ECG might change

during the patient’s evaluation: in the first phase, which occurs
within the initial 6 hours, changes in ST may be detected;2,14 the
second phase involves T-wave inversion, predominant from V1 to
V6 plus AVL with progressive deepening and QT prolongation;2

the third phase, occurring in weeks or months, shows a gradual res-
olution of T-wave and QT changes.2,14,13

There are no sex differences regarding ECG findings and bal-
looning pattern, whereas initially a lower left ventricular ejection
fraction has been reported in males.12 Furthermore, male patients
develop MACEs (i.e., cardiogenic shock, arrhythmias) more fre-
quently and have a higher in-hospital mortality rate. This increased
morbidity and mortality in the male population could be explained
by the stronger adrenergic drive required to initiate TS in men.
However, long-term mortality seems to be the same in both
sexes.12 A poor prognosis is usually associated with male sex,
advanced age, reduced left ventricular ejection fraction (below
35% at presentation), prolonged QT interval, atrial fibrillation, and
the development of acute complications (malignant arrhythmias,
syncope, and MACEs).7

The management of TS includes oxygen inhalation, intra-
venous heparin, aspirin, and β-blockers. Targeted therapies are not
available for TS. The use of β-blockers is reasonable due to the fre-
quent occurrence of high catecholamine levels. Many studies
reported that Angiotensin-Converting Enzyme Inhibitors (ACE-Is)
and ARBs can be used as part of regional wall motion abnormality
management. Anticoagulation therapy should be continued even
after TC diagnosis confirmation, as it is useful in preventing pos-
sible embolic events.6,15

As observed, emotional factors play a significant role in the
etiology of TS. However, also traumatic events seem to have a
great impact on the onset of TS, as reported in the present case.
Ghadri et al. suggested a new classification in order to predict
short- and long-term outcomes. Class I includes TS related to emo-
tional stress; class II encompasses cases secondary to physical
activities / medical procedures and neurological disorders; and,
finally, class III includes those patients without an identifiable trig-
gering factor.16 It has been found that the degree of catecholamine
surge is more severe in patients with physical or neurological trig-
gers than in those with emotional triggers. The highest mortality
was registered in TS patients secondary to neurological issues.3,4,16

In the literature, TS related to traumatic events is mostly linked to
traumas (road accidents and falls) involving the head, chest, and
lower limbs.4,16 There is no clear linear correlation between the
type or severity of trauma and TS. However, Fernandez et al.
found that TS was reported in all Glasgow Coma Scale (GCS) lev-
els but more commonly in those with GCS > 13 or < 8. There are
two subsets of patients with trauma at risk to develop TS, namely
those with GCS > 13 related to lower limb or chest injuries, and
those with GCS < 8 and head injury.4 The indicative average age
seemed to be 48 (age ranged from 1 to 83 years old) with a female
prevalence. According to our knowledge, the majority of ECG and
echocardiographic findings were consistent with the classical pat-
tern, while four cases related a reverse echocardiographic pat-
tern.17,20 By screening the literature, no previous cases associated a
humerus fracture with TS, whereas the general involvement of the
upper limbs has been reported in this condition.4

Conclusions
TS can present in various clinical scenarios. In line with the lit-

erature, in our case physical stressors are one of the main predis-

                                                                                                                  Case Report

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posing factors for TS occurrence. MACEs and poor short-term
prognosis usually affect more men than women with TS; however,
in the herein reported patient, the outcome was uneventful. Since
presenting symptoms may be not clear, any patient with trauma
should be monitored via ECG to allow for an early detection of TS.
A 24-hour observation is recommended in patients with TS-related
predisposing factors (i.e., age over 45 and comorbidities such as
hypertension, diabetes, pulmonary disease, malignancies, and
smoking habit) even if they present to the Emergency Department
with mild to moderate trauma.

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