CRVASA-370; No.

of Pages 12

cor et vasa xxx (2016) e1–e12

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journal homepage: http://www.elsevier.com/locate/crvasa

Review article – Special issue: Acute Stroke

The role of echocardiography in patients after

ischemic stroke

Martin Hutyra a,*, Luděk Pavlů a, Daniel Šaňák b, Jan Přeček a,

Martin Köcher c, Zbyněk Tüdös c, Tomáš Skála a, Ondřej Moravec a,
David Vindiš a, Miloš Táborský a
a
Department of Internal Medicine 1 – Cardiology, University Hospital Olomouc, Czech Republic
b
Department of Neurology, University Hospital Olomouc, Czech Republic
c
Department of Radiology, University Hospital Olomouc, Czech Republic

article info abstract

Article history: Therapy of acute phase of ischemic central vascular accident is focused on immediate actions
Received 2 December 2015 to suppress the severity of damage with the earliest possible initiation of reperfusion strategy
Received in revised form together with initiation and maintenance of adequate therapy to prevent further cerebral
6 February 2016 reinfarctions. The key factor for adequate and effective secondary prevention is elucidation of
Accepted 9 February 2016 the etiology of ischemic central vascular accident because the risk of brain reinfarction is the
Available online xxx highest in the first weeks after the primary event. The exclusion of potential cardiac or vascular
sources of embolization into the cerebrovascular system is essential in choosing adequate
Keywords: secondary prevention. Origins of embolization are important to identify because they repre-
Ischemic stroke sent different thromboembolic risks. Transesophageal echocardiography is a frequently used
Echocardiography diagnostic method after ischemic stroke. However, because of the variability in the frequency
Computed tomography of cardiac findings between studies of similar populations, the lack of correlation between
Magnetic resonance imaging cardiac abnormalities thought to be associated with each other and cryptogenic stroke, it is
Cardioembolic sources unclear if routine use of echocardiography in patients with cryptogenic stroke should be
Prophylaxis recommended. Its routine use to elucidate the causes of stroke has a role in some patient
groups, especially in young patients who present with cryptogenic stroke and no cardiovas-
cular risk factors, as well as in the setting of a deep venous thrombosis, and older patients with
a suspicion for structural heart disease or left ventricular or left atrial thrombus.
# 2016 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights
reserved.

Contents

Left atrium thrombi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

Thrombi in the left ventricle and on left-sided heart valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Paradoxical embolization through abnormal interatrial septum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

* Corresponding author at: Department of Internal Medicine 1 – Cardiology, University Hospital Olomouc, I. P. Pavlova 6, 775 20 Olomouc,
Czech Republic. Tel.: +420 604454222.
E-mail address: martinhutyra@seznam.cz (M. Hutyra).
http://dx.doi.org/10.1016/j.crvasa.2016.02.003
0010-8650/# 2016 The Czech Society of Cardiology. Published by Elsevier Sp. z o.o. All rights reserved.

Please cite this article in press as: M. Hutyra et al., The role of echocardiography in patients after ischemic stroke, Cor et Vasa (2016), http://
dx.doi.org/10.1016/j.crvasa.2016.02.003
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e2 cor et vasa xxx (2016) e1–e12

Paradoxical embolization through persistent left superior vena cava . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

Mitral valve annular calcification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Cardiac tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Ethical statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Funding body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

The essential prerequisite for adequate and effective second- patients, the AF prevalence reaches 5%. The octogenarians'
ary prevention is recognition of a cause of ischemic cerebro- population carries 10% AF prevalence. More than two thirds of
vascular accident (CVA) because the highest risk of repetition all atrial cases represent patients between 65 and 85 year of age
of cerebral ischemic event is during the first few weeks after and the median of age of a patient with AF is set at age of 75. AF
the primary CVA. is more frequent in men than in women, though men
Therapy of an acute phase of CVA is focused on immediate represent roughly a half of all atrial fibrillation patients due
actions to limit further brain damage with the earliest possible to their shorter life span. Atrial flutter is the second most
initiation of reperfusion strategy. The next immediate step is common supraventricular arrhythmia and also has age-
to initiate secondary prevention. It is to establish an adequate dependent incidence which oscillates from 0.005% in patients
pharmacotherapy to prevent further cerebrovascular acci- aged 50 years or younger to 0.59% in patients above the age of
dents. 80. Atrial flutter is 2.5 times more frequent in men than in
A search for possible origins of thromboembolism is an women and again occurs more frequently in patients with
integral part of management of ischemic stroke [1,2]. Current structural heart disease or in patients suffering from chronic
published data suggest the need for basic categorization of obstructive pulmonary disease (Table 2). Of importance, there
possible origins of thromboembolism according to the pre- is no difference in risk of thromboembolic event in between
sumed risk of a tromboembolic event. There are high risk permanent and paroxysmal forms of both AF and atrial flutter.
origins as well as the intermediate and low risk origins The risk of formation of thrombi in left atrium or left atrial
(Table 1) [3,4]. appendage is virtually identical (Figs. 1 and 2).
There is well established relation between AF and ischemic
Left atrium thrombi cerebrovascular accidents which represent about 85% of all
thromboembolic events in patients with AF. Vice versa, AF is
considered to be a cause of 16% of all ischemic cerebrovascular
(incidence: high, thromboembolic risk: high, prophylaxis: phar- accidents. Ten percent of ischemic cerebrovascular accident
macotherapy) sufferers have left atrium thrombi found in the left atrium. It
represents the two thirds of all patients suffering ischemic
Atrial fibrillation (AF) is the most frequent arrhythmia with stroke due to AF. AF is a cause of almost 80% of all
exponentially increasing prevalence with age and in individu- thromboembolic cerebrovascular accidents (CVA). AF is
als with structurally damaged heart. Prevalence of atrial associated with five times higher risk of CVA, two times
fibrillation in non-selected population is estimated in rather higher risk of death (due to CVA or heart failure) and finally it is
broad estimated range of 1–6%. In the seventh decennium aged associated with higher risk of vascular cognitive deficit in
comparison to healthy controls. Ischemic cerebrovascular
accidents due to AF are associated with the worse functional
outcomes and higher risk of death in comparison to other
Table 1 – Cardio-embolic sources.
Prophylaxis/ Medium-high Low
incidence
Anticoagulation Atrial flutter/ Thrombi in the left Table 2 – Clinical prediction rule for estimating the risk of
fibrillation ventricle and on left- stroke in patients with non-rheumatic atrial fibrillation
sided heart valves (AF) associated with thromboembolic event using
Spontaneous CHA2DS2-VASc score.
echocontrast
CHA2DS2-VASc Score
Prosthetic mechanical
valves C Congestive heart failure 1
Non-pharmacological Patent foramen Persistent left H Hypertension 1
ovale, septal superior vena cava A2 Age > 75 2
defects Intracardiac tumors D Diabetes mellitus 1
Infective endiocarditis S2 Stroke 2
Pulmonary V Vascular disease 1
arteriovenous A Age 65–74 1
malformations Sc Sex category – female 1

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Fig. 1 – Electrocardiography – atrial fibrillation.

Fig. 2 – Left atrial thrombus before (A) and 3 months after initiation of anticoagulation (B) on transesophageal
echocardiography.

causes of ischemic stroke. It can be explained by more frequent
closures of major brain vessels together with older age and
higher burden of other major comorbidities in this cohort. The
risk of cerebrovascular accident in patients with AF progres-
sively increases with age. There is 1–5% risk of CVA in 50–59
year old cohort and on the other hand up to 23–25% risk in
cohort of 80 year old and above. The annual risk of stroke in
patients suffering of AF is 2% but in the presence of other risk
factors the risk climbs above 10%. The most significant risk
factor is a prior cerebrovascular accident or transient ischemic
attack (relative risk [RR] 2.5) followed by older age (RR 1.4,
increasing by 1.3–1.6 with a decade), arterial hypertension (RR
1.9), systolic BP > 160 mmHg (RR 1.4) and diabetes (RR 1.7).
The annual incidence of thromboembolic complications in
patients with AF without the prophylaxis is 6% of average
(span of 1.9–12.3%/year). Metaanalysis of studies focusing on
reduction of ischemic cerebrovascular accidents with the
anticoagulation therapy found 62% risk relative risk reduction,
2.7% absolute risk reduction in primary prevention and 8.4 in
secondary prevention. The number to treat to limit one
ischemic stroke taking into the account the rate of cerebro-
vascular hemorrhage is 37. The prevalence of moderate to
severe forms of hemorrhage in patients treated with warfarin
is 3–5%, with annual incidence of 0.4%.
The decision when to commence prophylaxis in patients
with AF or atrial flutter is based on risk stratification of
thromboembolic events together with assessment of cost/
benefit from the broader perspective. The risk of thromboem-
bolic event, the assessment of risk of hemorrhage and last but
not least assessment of ability of a given patient to cooperate
are necessary to reach adequate compliance and safety.
Therefore, there are scoring tools enabling us to evaluate

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e4 cor et vasa xxx (2016) e1–e12
thromboembolic and hemorrhage risks. CHA2DS2VASc score is
well-established uncomplicated scoring system providing a
reliable estimate of a risk of thromboembolic event in patients
with AF. Individual acronyms are: C – congestive heart failure,
one point; H – arterial hypertension, one point; A – age of 75 or
older, two points; D – diabetes mellitus, one point; S – prior
stroke/transient ischemic accident, two points; V – vascular
disease (prior myocardial infarction, coronary artery disease,
peripheral vascular disease), one point; A – age above 65, one
point; Sc – sex category – female, one point. These points add
up to a final score. CHA2DS2VASc score of two or above is
unequivocal indication for anticoagulation therapy in the
absence of contraindications. Patients with one point based on
CHA2DS2VASc score benefit out of anticoagulation therapy as
well. Patients with zero points are not indicated for antic-
oagulation therapy.
Approximately 20% of all patients indicated for antic-
oagulation therapy have higher than acceptable risk of
hemorrhage or expected low compliance to anticoagulation
therapy. Registry data suggest that more than a half of high
risk patients are not for the above mentioned reasons treated
with anticoagulation therapy. Furthermore, the standard of
care therapy is warfarin with its relatively very narrow
therapeutic window of INR (international normalized ratio) of
2–3. Unfortunately, the INR levels above 3.0 (especially above
5.0) are associated with exponential increase in hemorrhagic
risk, potentially risk of death.
Transesophageal echocardiography (TEE) brings a substan-
tial increase in sensitivity in relation to exclusion of
cardioembolic origins of ischemic stroke in comparison to
transthoracic echocardiography (TTE). Besides high sensitivity
and specificity for detection of thrombi in the left atrial
appendage (LAA) and in the left atrium, TEE also provides
valuable information of other independent risk factors of
systemic thromboembolism in patients with AF: systolic
dysfunction of left ventricle (ejection fraction of less than
35%), spontaneous echocontrast in left-sided heart chambers,
limited left atrial appendage flow velocity (less than 20 cm/s),
severe atherosclerosis of the ascending aorta and calcification
of left sided heart valves.
Fig. 3 – Left ventricular thrombi (red arrows) before (A) and after (B) initiation of anticoagulation therapy on apical
four-chamber view.
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The most common site of intracardiac thrombosis in
patients with AF is left atrial appendage (90% of all left atrium
thrombi). Therefore, surgical techniques of LAA removal as an
additional procedure to other cardiothoracic surgeries were
developed hand in hand with percutaneously placed occlusion
devices. The mechanical LAA occlusion systems are indicated
in patients with non-valvular AF and high risk of thromboem-
bolism with contraindication to standard anticoagulation
therapy. In this clinic scenario the mechanical occlusion
systems reach the same efficacy as anticoagulation therapy
with warfarin [5–16].
Thrombi in the left ventricle and on left-sided heart
valves
(incidence: low, thromboembolic risk: high, prophylaxis: surgical
and pharmacotherapy)
Ventricular free wall rupture represents a feared mechani-
cal complication of acute myocardial infarction (MI) occurring
in 1–6% of patients. It is considered to be the cause of death in
7–20% of fatal myocardial infarctions. It is worth mentioning
that the above statistics are derived from thrombolysis era of
MI therapy. It is generally accepted that the incidence of free
wall myocardial rupture is lower in the era of percutaneous
coronary interventions (Figs. 3 and 4).
The most feared clinical scenario leads to immediate death
but in some cases the rupture is covered by pericardium that
prevents acute tamponade resulting in formation of pseudoa-
neurysm. Therefore, the wall of pseudoaneurysm differs from
proper aneurysm that has myocardium or at least a scar
incorporated. Pseudoaneurysm is a rare finding which is
suggested prevalence of 0.2% among all patients with acute
myocardial infarction. The most common form of pseudoa-
neuryms manifestation is heart failure (36%), chest pain (30%)
and dyspnea on exertion (20%). Sudden death represents 3% of
presentation of pseudoaneurysm and circa 12% of cases present
without any symptoms. Among rare pseudoaneurysm pre-
sentations are symptoms of heart arrhythmia or CVA due to
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cor et vasa xxx (2016) e1–e12 e5

Fig. 4 – Thrombus in left ventricular pseudoaneurysm. Echocardiography–thrombus in apical four and two chamber views
(A, B) in left ventricular posterbasal pseudoaneurysm due to free wall rupture is evident (red arrows). Contrast enhanced
cardiac magnetic resonance imaging (C) PSIR-TrueFisp 2D reconstruction. (LV, left ventricle; RV, right ventricle; PA
pseudoaneurysma; T, thrombus.)

systemic embolization. Most of patients are admitted to
hospital within 3–80 days post prior acute myocardial infarction.
The risk of rupture of already diagnosed pseudoaneurysm
exceeds 45%, and the surgical repair mortality does not reach
10% in comparison to 48% mortality in patients unable to
undergo surgical treatment. 1–2.5% patients with acute myo-
cardial infarction suffer systemic embolization into the cerebral
circulation due to formation of thrombus in first month after MI,
and half of them suffer stroke in first 5 days of myocardial
infarction. The risk increases with the severity of damage to
global systolic function and with the extent of regional wall
motion abnormalities.
Aneurysms of left ventricle are a dyskinetic bulge of left
ventricle (LV) with a broad entry between the LV cavity and the
aneurysms. Aneurysm has normally formed wall of maocar-
dium consisting of endocardium, myocardium and epicardiac
tissue. This differs from pseudoaneurysm with a wall composed
of pericardial tissue together with thrombotic tissue. The wall
motion abnormality is a technical term for hypokinetic or
akinetic segments of left ventricle and leads to global systolic
dysfunction. Patients with LV systolic dysfunction are in
increased risk of thrombus formation with estimated 1.8% risk
of CVA in first one year after myocardial infarction, and 4.7% risk
in first 5 years after myocardial infarction.
Chronic congestive heart failure delivers 2–3-fold in-
crease in relative risk of CVA. Clinically silent brain
embolizations are detectable up to 40% of heart failure
patients. Retrospective study of Fuster et al. showed 18%
incidence of thromboembolic cerebrovascular accidents in
patients suffering from dilated cardiomyopathy without
anticoagulation therapy in comparison to no case of CVA in
patients treated with anticoagulation. Other prospective
study demonstrated only 3% incidence of arterial thrombo-
embolism in 264 heart transplant candidates with LV
ejection fraction of less than 20% in average 1 year
follow-up period. The incidence of magnetic resonance
detected thrombi in ventricles in non-selected population of
ischemic cardiomyopathy patients with systolic dysfunction
(ejection fraction less than 50%) has been found to be 7%.
The risk of thrombus in left ventricle is associated with
more severe left ventricular systolic dysfunction (EF LV
under 30%) and prior myocardial infarction.
The incidence of prior ischemic CVA in patients with left
ventricle thrombus is estimated to be 12%. Non-compaction
cardiomyopathy, restrictive cardiomyopathy and Löffler's
endocarditis represent specific entities with increased risk
of intraventricular thrombi formation.
Echocardiography remains the basic diagnostic method to
diagnose pseudoaneurysm of left ventricle. The common
associated finding of pseudoaneurysm is a pericardial separa-
tion above 5 mm; only rarely it is possible to visualize rupture
in free myocardial wall. The definitive diagnosis is preferably

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made with computed tomography or contrast magnetic
resonance imaging (MRI).
The imaging of ventricular aneurysm in two-dimensional
imaging demonstrates bulky large dyskinetic structure localized
in area of prior myocardial infarction with a broad entry channel
and in case of optimal visibility one can appreciate hyperecho-
genic mural thrombus. Contrast enhanced MRI elucidates
definitive morphology of aneurysm together with localization
and extent of delayed enhancement that correlates well with
usually transmural extent of non-viable myocardial scar tissue.
Regional wall motion abnormalities and assessment of
global ejection fraction of left ventricle are usually assessed
with standard two-dimensional transthoracic echocardiogra-
phy (TTE) with a possibility to imagine intraventricular
thrombi. To improve sensitivity and specificity of a TTE
echographic contrast can be used. This method demonstrates
more accurate and reliable results in detection of intracardiac
thrombi in comparison to standard TTE study.
The presence of LV thrombus mandates anticoagulation
therapy together with follow-up imaging studies. There is
generally accepted consensus on duration of anticoagulation
therapy after the thrombus disappearance. Of course, the
optimal situation would be effective therapy of the causative
disease that predispose to thrombus formation.
Anticoagulation therapy is not indicated in individuals
with LV systolic dysfunction without the proof of intraventric-
ular thrombus or AF. The therapy aimed at optimal reversal of
systolic dysfunction (revascularization in ischemic cardiomy-
opathy, biologic treatment of Löffler's endocarditis). Surgical
treatment is recommended for left ventricular pseudoaneur-
ysms [17–19].
Paradoxical embolization through abnormal
interatrial septum
(incidence: low, thromboembolic risk: probably low, prophylaxis:
surgical or percutaneously placed devices)
Foramen ovale patent (PFO) is a physiologic variety
specified by the presence of minimal interatrial shunt in
between lamina of interatrial septum with prevalence of
Fig. 5 – (A) Patent foramen ovale with minimal right to left shunt (arrow). (B) Appearance of the Amplatzer septal occluder
device on control TEE examination during the procedure. (LA, left atrium; RA, right atrium.)
Please cite this article in press as: M. Hutyra et al., The role of echocardiography in patients after ischemic stroke, Cor et Vasa (2016), http://
dx.doi.org/10.1016/j.crvasa.2016.02.003
17–27% in non-selected population with gradual decrease of
prevalence in older age. It is a small channel with a variable
shape which is localized in between the lamina of septum
primum and septum secundum. This remnant structure
provides a direct flow of blood from vena cava inferior directly
toward left sided heart chambers in embryonal period. From
the functional standpoint foramen ovale at the normal
situation is closed or there is hemodynamically non-signifi-
cant left to right shunt which is not constant. In specific
situations there is a bidirectional blood flow across PFO. In case
of permanent (precapillary form of pulmonary hypertension)
or transient (Valsalva maneuver, cough) elevation of right
atrium pressure, there is an accentation of right to left
shunting. Based on autopsy findings and on echocardiographic
studies, PFO is a common finding with 27% prevalence in
general population (Figs. 5 and 6).
Cryptogenic etiology of ischemic CVA is found in nearly 50%
patients below the age of 55 years and approximately in 25%
individuals with ischemic CVA in all age groups. Cryptogenic
etiology means that there is no evidence of intracardiac
thrombi, arterial origin of embolization and there is no
evidence of atherosclerosis of intracranial brain vessels.
There is relatively substantial evidence in literature
proving association in between cryptogenic CVA and PFO
(OR 3.1) or association in between aneurysm of left atrium
and cryptogenic CVA (OR 6.1) in all age groups. Though the
results of published observational studies are not unequiv-
ocal, there are well known associations that suggest the
causal relations in between the cryptogenic recurrent CVA
and the presence of PFO, PGO morphology, the amount of
right to left shunt in particular in younger aged group of
patients under the age of 55.
The basic pathophysiologic mechanism for the above
associations is paradoxical embolization from the venous
system through the PFO. The morphology of PFO is one of the
substantial determinants of a risk of ischemic CVA. Other
possibilities of embolization into the cerebral circulation are
in situ thrombosis directly in PFO channel caused by limited
blood flow or due to hypercoagulable state.
The basic prerequisite for the paradoxical embolization is
transient or permanent increase in right atrial pressure that
enable the transfer of thromboembolic mass through the PFO.
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cor et vasa xxx (2016) e1–e12 e7

Fig. 6 – Transesophageal echocardiography (A) of sinus venosus atrial septal defect (red arrowhead) between the left atrium
and the origin of the superior vena cava and the anomalous connection of pulmonary veins entering at the superior vena
cava (red stars) on computed tomography – CT (B, C) and CT angiography (D). (LA, left atrium; RA, right atrium; IAS, interatrial
septum; SVC, superior vena cava; Ao, aorta; RUPV, right upper pulmonary vein; RLPV, right lower pulmonary vein.)

In individuals suffering from acute pulmonary embolism the
risk of paradoxical embolization is higher for two reasons.
First, there is a higher probability of the presence of origin of
emboli in venous system. Second, there is a high probability of
increased right atrial pressure by pulmonary hypertension due
to pulmonary hypertension. The prevalence of PFO with right
to left shunt is described in 35% acute pulmonary patients. The
group with proven right to left shunt has clearly doubled the
risk of in-hospital mortality (13% vs. 2.2%). Patent foramen
ovale with bidirectional flow is associated with a risk of
clinically silent CVA as evidenced by brain MRI (33% vs 2.2%).
Clinical manifestation of paradoxical embolization is not
limited to cerebral vessels only. There are well documented
cases of coronary vessel embolization and embolization into
the peripheral vascular system.
Atrial septum defect is the most common inherited heart
defect detected in adulthood. The clinical manifestation may be
associated with paradoxical embolization into the cerebral
vessels. The most frequent variant of atrial septum defect is the
septum secundum atrial defect localized in central part of atrial
septum. It represents approximately ¾ of all atrial septum
defect cases. The other variants (sinus venosus superior and
inferior defect) are less frequent. Nevertheless, it is important to
consider them and to use contrast TEE to visualize them in hard
to visualize cases. The rapid passing of contrast material into
the left sided heart chambers is typical finding.
The contrast (agitated normal saline or colloid) transeso-
phageal echocardiography is considered to be a gold standard
imaging method. It is important to test repeatedly in rest and
during the provocative maneuvers. It is necessary to visualize

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properly the PFO channel during the passing of contrast
material to be able to detect a minimal amount of bubbles
passing through. The morphology of PGO together with
meticulous description of characteristics of the flow through
the PFO is able to provide semiquantitative assessment of the
severity of shunt. The detection of more than 20 (25)
microbubbles of contrast material into the left atrium suggests
relatively severe right to left shunt. The question of optimal
timing of PFO percutaneous device closure is not elucidated.
The routine approach to close all PFOs after prior cryptogenic
CVA is not recommended. Based on published evidence, there
is no substantial benefit of reduction of embolic CVA in
comparison to prophylactic pharmacotherapy.
The current data support the indication for percutaneous
closure in patients with repeated cryptogenic ischemic CVA
with the suspection for paradoxical embolization, especially in
cases in which there is evidence for disease causing right
atrium pressure increase (for example pulmonary embolism)
or there is evidence of deep vein thrombosis. The exclusion of
an alternative cause of ischemic stroke (e.g., aortic arch
disease) may be important in patients considering patent
foramen ovale closure.
The evidence of repeated CVA can be provided by typical
MRI brain findings of prior silent CVAs. If there is no
evidence or suggestion of RA pressure elevation, the
indication should be thoughtfully considered in younger
patients (less than 55 year old) with severe right to left shunt
and large atrial septal defect. Percutaneous or surgical atrial
septal defect closure is indicated in case of hemodynami-
cally significant left to right pressure (Qp/Qs > 1.5), right
ventricular dilatation, pulmonary hypertension, in atrial
septal defect above 10 mm. The prior ischemic CVA with
clear paradoxical embolization pathophysiology etiology is
also an indication for closure.
Indication for specific pharmacotherapy of PFO (antic-
oagulation or antiaggregation therapy) as prophylaxis of
ischemic CVA is not clearly defined. Rationally, it appears to
use standard dose and treatment of prophylaxis of ischemic
CVA especially in cases of proved coincidence of deep vein
thrombosis and left atrium aneurysm [20,21].

Fig. 7 – Contrast enhanced echocardiography. (A) After injecting agitated saline into the right antecubital vein, there was a
normal sequence of opacification of the right heart chambers with no penetration of microbubbles into the left heart
chambers. (B, C) In the apical four-chamber and midesophageal bicaval transesophageal views of the patient lying on the left
side, synchronous saturation of the left and right heart chambers was noticeable after applying a contrast agent into the left
antecubital vein. There was no evidence of echocontrast agent flow from the region of the non-dilated coronary sinus into
the left or right atrium. (D) Transesophageal echocardiography examination focused on the pulmonary vein revealed a clear
inflow of the contrast agent into the left atrium through the left superior pulmonary vein (white arrow). (LA, left atrium; RA,
right atrium; IAS, interatrial septum; SVC, superior vena cava; AoV, aortic valve; LUPV, left upper pulmonary vein.)

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Paradoxical embolization through persistent left
superior vena cava
(incidence: low, thromboembolic risk: high, prophylaxis: surgical
or percutaneously placed devices)
A persistent left superior vena cava (PLSVC) is the most
common anomaly involving central venous return in the thorax
with an estimated prevalence of 0.3% in the general population
and 4–10% in patients with congenital heart disease. Most
commonly (90%), the PLSVC drains through the coronary sinus
into the right atrium and this form is not associated with
increased risks inherent with a right-to-left shunt such as
embolic cerebrovascular events. Rarely (<10%), the PLSVC drains
into the left atrium, typically through an unroofed coronary
sinus and very seldom directly or through the pulmonary vein.
This form is characterized by the presence of a right-to-left
shunt associated with a relatively high risk of air or septic
embolism or thromboembolism in the systemic circulation. The
suggested pathogenetic mechanism for brain ischemia and
stroke is paradoxical embolism through a right-to-left shunt,
with the possible embolic source in the left upper extremity
veins (Figs. 7 and 8).
As to the diagnosis, a simple diagnostic procedure such
as contrast echocardiograhy with a contrast agent injected
into the left upper extremity venous system should be used.
It may reveal simultaneous left and right atrium opacifica-
tion consistent with an intracardiac right-to-left shunt.
Contrast TEE (with obligatory left antecubital vein contrast
agent application) is the favored screening modality for
cardiac sources of systemic embolism and should be
performed routinely in all young patients without an
evident cause of ischemic stroke. Right upper extremity
intravenous contrast agent application should not be used
to detect the PLSVC.
Moreover, the contrast agent should be injected into the left
upper extremity venous system with various positions of the
extremity (elevated/along the body) as well as the body
(lateral/supine). This is because the flow through the PLSVC
may be position-dependent. With the exception of cardiac
thrombus, spontaneous echo contrast, vegetations and
tumors, other pathological findings such as a right-to-left
shunt through an atrial septal defect, patent foramen ovale,
pulmonary arteriovenous malformations and congenital
anomalies of thoracic venous circulation such as a PLSVC
connected through the left upper pulmonary vein to the left
atrium may be identified as a pathway for paradoxical
embolization.
Endovascular approaches to the treatment of patients with
a symptomatic PLSVC and right-to-left shunt using the
Amplatzer occluder or coil embolization are only sporadically
reported in the literature [22].
Mitral valve annular calcification
(incidence: low, thromboembolic risk: intermediate, prophylaxis:
pharmacological/surgical)
Mitral annular calcification is a chronic degenerative
process, progressing with advancing age. It is more common
in women and in people over 70 years old (Fig. 9).
The presence of asymptomatic mitral annular calcifica-
tion (MAC) does not require specific medical therapy.
Because of the association between MAC and atherosclero-
sis, valvular disease, stroke, and other vascular diseases,

Fig. 8 – Computed tomography. Reconstructed images using volume rendering (A) and a two-dimensional image (B)
demonstrate that the persistent left superior vena cava originates from the left brachiocephalic vein (white arrow) and drains
(yellow arrow) into the left upper pulmonary vein, which leads directly into the left atrium. (Ao, aorta; PA, pulmonary artery.)

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e10 cor et vasa xxx (2016) e1–e12

antithrombotic therapy. Patients with isolated MAC do not

require hospitalization. However, these patients are at
increased risk for major cardiovascular events (e.g., stroke,
myocardial infarction). Given the strong association with
atherosclerosis, cardiovascular risk factor modification (e.g.,
hypertension, hyperlipidemia) and appropriate follow-up
are important.

Cardiac tumors

(incidence: low, thromboembolic risk: high, prophylaxis: surgical)

Patients with cardiac tumors may present with cardiovas-

Fig. 9 – Mitral valve annular calcification.
appropriate medical management of concomitant cardio-
vascular risk factors is recommended. In patients with MAC
who have a single embolus documented to be calcific, data
are not sufficient to recommend either for or against
cular related or constitutional symptoms, but more often than
not a cardiac mass is discovered incidentally during an
imaging examination performed for an unrelated indication
[23] (Fig. 10).
Primary cardiac tumors are rare, with an autopsy
incidence ranging from 0.001% to 0.030%. They represent
an important group of cardiovascular abnormalities because
early and accurate diagnosis may be curative. Three-
quarters of these tumors are benign and nearly half of the

Fig. 10 – Cardiac tumors. Left atrium sarcoma on transesophageal (A) and a two-dimensional image (B) demonstrate lobulated
tumor (yellow arrow) sessile on interatrial septum/mitral valve respectively and reaching a diameter of 10 cm. Calcified left
atrial myxoma on computed tomography scan (C) and a two-dimensional image (D) demonstrates tumor (white arrow)
sessile on interatrial septum.

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cor et vasa xxx (2016) e1–e12
benign tumors are myxomas. Metastases to the heart are far
more common than primary cardiac tumors. Primary
[2]
cardiac tumors present with one or more of the symptoms
of the classic triad of: cardiac symptoms and signs resulting
from intracardiac obstruction; signs of systemic emboliza- [3]
tion; and systemic or constitutional symptoms [23].
Echocardiography is an ideal initial imaging modality since
it is simple, non-invasive, widely available, and low cost. [4]
Cardiac tumors are also diagnosed by use of magnetic
resonance or cardiac computed tomography imaging.
Whereas surgery is indicated in patients with benign [5]
tumors, systemic chemotherapy is indicated in those
who have widespread or unresectable malignant disease,
and chemotherapy and radiotherapy are usually combined
in treatment of patients with primary cardiac lymphomas [6]
[23].
Conclusion [7]
Transesophageal echocardiography is a frequently used
diagnostic method after ischemic stroke. However, because [8]
of the variability in the frequency of cardiac findings between
studies of similar populations, the lack of correlation between
[9]
cardiac abnormalities thought to be associated with each other
and cryptogenic stroke, it is unclear if routine use of
echocardiography in patients with cryptogenic stroke should
be recommended [3,24].
However, its routine use to elucidate the causes of stroke [10]
has a role in some patient groups, especially in young
patients who present with cryptogenic stroke and no
cardiovascular risk factors, as well as in the setting of a [11]
deep venous thrombosis, and older patients with a suspi-
cion for structural heart disease or left ventricular or left
atrial thrombus [3,24]. [12]
Conflict of interest [13]
No conflict of interest.
[14]
Ethical statement
I declare, on behalf of all authors that the research was
conducted according to Declaration of Helsinki. [15]
Funding body
[16]
This study was supported by the Research Grants of the
Ministry of Health of the Czech Republic (NT 11046-6/2010 and
NT14288-3/2013) and by IGA LF UP 2016-018.
[17]
references
[18]
[1] M. Kral, R. Herzig, D. Sanak, et al., Prevention of
cardioemboligenic stroke in the Olomouc region of the
Please cite this article in press as: M. Hutyra et al., The role of echocardiography in patients after ischemic stroke, Cor et Vasa (2016), http://
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e11
Czech Republic, Journal of the Neurological Sciences 285
(Suppl. 1) (2009) S160.
M. Král, D. Šaňák, T. Veverka, et al., Troponin T in acute
ischemic stroke, American Journal of Cardiology 112 (1)
(2013) 117–121.
E. Doufekias, A.Z. Segal, J.R. Kizer, Cardiogenic and
aortogenic brain embolism, Journal of the American College
of Cardiology 51 (2008) 1049–1059.
M. Pepi, A. Evangelista, P. Nihoyannopoulos, et al.,
Recommendations for echocardiography use in the
diagnosis and management of cardiac sources of embolism,
European Journal of Echocardiography 11 (2010) 461–464.
K. Kimura, K. Minematsu, T. Yamaguchi, Atrial fibrillation
as a predictive factor for severe stroke and early death in
15,831 patients with acute ischaemic stroke, Journal of
Neurology, Neurosurgery and Psychiatry 76 (2005) 679–683.
E.M. Hylec, A.S. Go, Y. Chang, N.G. Jensvold, et al., Effect of
intensity of oral anticoagulation on stroke severity and
mortality in atrial fibrillation, New England Journal of
Medicine 349 (2003) 1019–1026.
M. O'Donnell, W. Oczkowski, J. Fang, et al., Influence of pre-
admission antithrombotic therapy on stroke severity in
patients with atrial fibrillation: an observational study, The
Lancet Neurology 5 (2006) 749–754.
E.M. Arsava, E. Ballabio, T. Benner, et al., The causative
classification of stroke system, Neurology 75 (2010)
1277–1284.
J. Friberg, H. Scharling, N. Gadsboll, T. Truelsen, Jensen,
et al., Comparison of the impact of atrial fibrillation on the
risk of stroke and cardiovascular death in women versus
men (The Copenhagen City Heart Study), American Journal
of Cardiology 94 (2004) 889–894.
Y. Miyasaka, M.E. Barnes, K.R. Bailey, et al., Mortality trends
in patients diagnosed with first atrial fibrillation: a 21-year
community-based study, Journal of the American College of
Cardiology 49 (2007) 986–992.
D. Conen, C.U. Chae, R.J. Glynn, et al., Risk of death and
cardiovascular events in initially healthy women with new-
onset atrial fibrillation, JAMA 305 (2011) 2080–2087.
D. Šaňák, R. Herzig, M. Král, et al., Is atrial fibrillation
associated with poor outcome after thrombolysis? Journal
of Neurology 257 (6) (2010) 999–1003.
T.S. Potpara, M.M. Polovina, M.M. Licina, et al., Reliable
identification of truly low thromboembolic risk in patients
initially diagnosed with alone atrial fibrillation: the
Belgrade atrial fibrillation study, Circulation: Arrhythmia
and Electrophysiology 5 (2012) 319–326.
T.S. Potpara, G.R. Stankovic, B.D. Beleslin, et al., A 12-year
follow-up study of patients with newly diagnosed alone
atrial fibrillation — implications of arrhythmia progression
on prognosis: the Belgrade Atrial Fibrillation study, Chest
141 (2012) 339–347.
D.R Holmes Jr., S.K. Doshi, S. Kar, et al., Left atrial
appendage closure as an alternative to warfarin for stroke
prevention in atrial fibrillation: a patient-level meta-
analysis, Journal of the American College of Cardiology 65
(2015) 2614–2623.
J. Camm, G.Y.H. Lip, D. Atar, et al., 2012 focused update of
the ESC Guidelines for the management of atrial fibrillation,
European Heart Journal 33 (2012) 2719–2747. , http://dx.doi.
org/10.1093/eurheartj/ehs253.
V. Fuster, B.J. Gersh, E.R. Giuliani, et al., The natural history
of idiopathic dilated cardiomyopathy, American Journal of
Cardiology 47 (1981) 525–531.
M. Hutyra, T. Skala, D. Marek, et al., Acute severe mitral
regurgitation with cardiogenic shock caused by two-step
complete anterior papillary muscle rupture during acute
myocardial infarction, Biomedical papers of the Medical
CRVASA-370; No. of Pages 12

e12 cor et vasa xxx (2016) e1–e12

Faculty of the University Palacký , Olomouc, Czechoslovakia
150 (November (2)) (2006) 293–297.
[19] M. Hutyra, T. Skála, M. Kamínek, D. Horák, J. Lukl, Význam
stanovení viability myokardu před revaskularizací u
pacientů s ischemickou kardiomyopatií a systolickou
dysfunkcí levé komory srdeční, Vnitrni Lekarstvi 54 (April
(4)) (2008) 395–401.
[20] B. Meier, B. Kalesan, H.P. Mattle, et al., Percutaneous closure
of patent foramen ovale in cryptogenic embolism, New
England Journal of Medicine 368 (2013) 1083–1091. , http://
dx.doi.org/10.1056/NEJMoa1211716.
[21] J.D. Carroll, J.L. Saver, D.E. Thaler, Closure of patent foramen
ovale versus medical therapy after cryptogenic stroke, New
England Journal of Medicine 368 (2013) 1092–1100. , http://dx.
doi.org/10.1056/NEJMoa1301440.
[22] M. Hutyra, T. Skála, D. Šanák, et al., Persistent left superior
vena cava connected through the left upper pulmonary
vein to the left atrium: an unusual pathway for paradoxical
embolization and a rare cause of recurrent transient
ischaemic attack, European Journal of Echocardiography
(2010), http://dx.doi.org/10.1093/ejechocard/jeq079.
[23] J. Butany, V. Nair, A. Nassemudin, et al., Cardiac tumours:
diagnosis and management, The Lancet Oncology 4 (6)
(2005) 219–228.
[24] McGrath, R. Emer, et al., Transesophageal
echocardiography in patients with cryptogenic ischemic
stroke: a systematic review, American Heart Journal 168 (5)
(2014) 706–712, e14.

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