54 Current Cardiology Reviews, 2012, 8, 54-67
Acute Cardioembolic Cerebral Infarction: Answers to Clinical Questions*
Adrià Arboixa,b* and Josefina Alióc
a
Cerebrovascular Division, Department of Neurology, Capio-Hospital Universitari del Sagrat Cor, Universitat de Bar-
celona, Barcelona, Spain; bCIBER de Enfermedades Respiratórias (CB06/06). Instituto Carlos III, Madrid; cDepartment
of Cardiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
Abstract: Cardioembolic cerebral infarction (CI) is the most severe subtype of ischaemic stroke but some clinical aspects
of this condition are still unclear. This article provides the reader with an overview and up-date of relevant aspects related
to clinical features, specific cardiac disorders and prognosis of CI. CI accounts for 1430% of ischemic strokes; patients
with CI are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate
treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of CI, including
sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke’s aphasia or global aphasia without
hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacu-
nar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely.
The most common disorders associated with a high risk of cardioembolism include atrial fibrillation, recent myocardial
infarction, mechanical prosthetic valve, dilated myocardiopathy and mitral rheumatic stenosis. Patent foramen ovale and
complex atheromatosis of the aortic arch are potentially emerging sources of cardioembolic infarction. Mitral annular cal-
cification can be a marker of complex aortic atheroma in stroke patients of unkown etiology. Transthoracic and trans-
esophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Hol-
ter monitoring. Magnetic resonance imaging, transcranial Doppler, and electrophysiological studies are useful to docu-
ment the source of cardioembolism. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as
compared with other subtypes of cerebral infarction. Secondary prevention with anticoagulants should be started immedi-
ately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor
compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. Dabigatran has been shown to be non-inferior to
warfarin in the prevention of stroke or systemic embolism. All significant structural defects, such as atrial septal defects,
vegetations on valve or severe aortic disease should be treated. Aspirin is recommended in stroke patients with a patent
foramen ovale and indications of closure should be individualized. CI is an important topic in the frontier between cardiol-
ogy and vascular neurology, occurs frequently in daily practice, has a high impact for patients, and health care systems and
merits an update review of current clinical issues, advances and controversies.
Keywords: Cardioembolic stroke, recurrent embolization, atrial fibrillation, cardiac source of emboli, outcome, oral anticoagu-
lation, heart failure.
1. THE CLINICAL RELEVANCE OF CARDIOEM- In the Sagrat Cor Hospital of Barcelona Stroke Registry,
BOLIC CEREBRAL INFARCTION the frequency of cardioembolic stroke is 18% [14], a similar
percentage than that in the studies of Bougousslavsky et al.
Stroke is the leading cause of disability and the second
[15] (16%) and Timsit et al. [16] (19.4%), higher than that
most common cause of death worldwide [1-3]. Accurate
reported by Vázquez et al. [17] (14%) and de Al-Rajed et al.
definition of the mechanism of stroke is crucial as this will [18] (14%), but lower than the percentages of Rothrock et al.
guide the most effective care and therapy. Cardioembolic
[19] (22%) and Norrving and Löwenhielm [20] (30.6%).
cerebral infarction accounts approximately for one quarter of
However, the incidence of cardioembolic cerebral infarction
all cerebral infarcts [4-8]. In most cases, recurrence of cardi-
increases with age [14]. In the subgroup of patients younger
oembolism can be prevented by oral anticoagulants. There-
than 65 years of age, cardioembolic cerebral infarction oc-
fore, for a patient with a cerebral infarct, early confirmation
curred in 14.6% of cases but in very old patients (age 85
of a diagnosis of cardioembolic cerebral infarction is ex- years) cardioembolic stroke reached 36% of cases and is the
tremely important in order to initiate anticoagulation therapy
most frequent ischaemic subtype (Table 1).
for an adequate secondary prevention [9-13].
Embolism from the heart to the brain results from one of
three mechanisms: blood stasis and thrombus formation in an
*Address correspondence to this author at the Cerebrovascular Division, enlarged (or affected by another structure alteration) left car-
Department of Neurology, Capio-Hospital Universitari del Sagrat Cor, diac chamber (e.g., left ventricular aneurysm); release of
Universitat de Barcelona, Viladomat 288, E-08029 Barcelona, Spain; material from an abnormal valvular surface (e.g., calcific
Tel: +34–93–4948940; Fax: +34–93–4948906; E-mail:
*This manuscript is an updated version of Arboix A, Alió J. Cardioembolic degeneration); and abnormal passage from the venous to the
stroke: clinical features, specific cardiac disorders and prognosis. Current arterial circulation (paradoxical embolism) [3]. Cardiac em-
Cardiol. Rev. 2010; 6: 150161. boli can be of any size, but those of arising from the cardiac
1573-403X/12 $58.00+.00 © 2012 Bentham Science Publishers
, Acute Cardioembolic Cerebral Infarction Current Cardiology Reviews, 2012, Vol. 8, No. 1 55
Table 1. Distribution of Cerebral Infarctions According to Age in the Sagrat Cor Hospital of Barcelona Stroke Registry
Subtype of cerebral Years of age
infarction < 65 65–74 (n=501) 75–84 85
(n = 1840) (n= 314) (n=722) (n=303)
Cardioembolic 46 (14.6) 100 (20) 213 (29.5) 109 (36)
Atherothrombotic 66 (21.0) 159 (31.7) 233 (32.3) 95 (31.4)
Lacunar 93 (29.6) 159 (31.7) 173 (24) 59 (19.5)
Unknown cause 61 (19.4) 69 (13.8) 81 (11.2) 37 (12.2)
Unusual cause 48 (15.3) 14 (2.8) 22 (3.0) 3 (1)
Percentages in parenthesis.
chambers are often large and hence especially likely to cause However, in many patients, history, physical examination,
severe stroke, disability and death. Cardioembolic cerebral and routine diagnostic tests (electrocardiogram and findings
infarction is the most severe ischaemic stroke subtype, with on neuroimaging studies) are sufficient to easily make the
high in-hospital mortality rate (6–27%) and a substantial diagnosis of most presumed cardiac emboligenic condition
number of patients with neurological dysfunction at the time (e.g., atrial fibrillation, recent myocardial infarction, heart
of hospital discharge; however, the risk of early embolic failure, prior rheumatic disease, splinter hemorrhages) [23].
recurrence varies between 1 and 10% [3,6,21,22] (Fig. 1). An important exception is paroxysmal atrial fibrillation,
which can be detected by 2448 hour Holter monitoring
immediately after stroke. However, 24-hour Holter may not
be sufficient for diagnosing paroxysmal atrial fibrillation and
there is evidence supporting the value of prolonged cardiac
monitoring. In a recent study of Gaillard et al. [24], tran-
stelephonic ECG monitoring increased detection rate of par-
oxysmal atrial fibrillation in stroke and TIA patients whose
24-hour Holter monitoring was unrevealing, especially if
they had frequent premature atrial ectopic beats, recent ante-
rior circulation infarct on MRI, or both. The implantation of
subcutaneous devices for up to 14 months of rhythm moni-
toring increases the detection of paroxysmal atrial fibrillation
[25]. Prolonged cardiac rhythm monitoring increases the
detection of paroxysmal atrial fibrillation.
Transthoracic echocardiogram can disclose structural
cardiopathies (dilated cardiomyopathies, mitral stenosis and
Fig. (1). Histopathological specimen showing a hemorrhagic cere- other structural ventricular diseases and intraventricular
bral infarction of a cardioembolic origin with signs of ventricular thrombus, vegetations or tumors) and enables measurement
displacement and brain herniation in the territory of the middle of the left atrial size and left ventricular systolic function
cerebral artery. [1,2,23]. Transesophageal echocardiogram is able to study
the aortic arch and ascending aorta, left atrium and left atrial
There is no gold standard for making the diagnosis of appendages, intra-arterial septum, pulmonary veins and
cardioembolic cerebral infarction. Neuroimaging findings valve vegetations [1-3,23]. Transesophageal echocardiogra-
that support cardioembolic stroke include simultaneous or phy is more likely to be helpful in young patients with
sequential strokes in different arterial territories. Owing to stroke, stroke of unknown cause and in patients with non-
their large size, cardiac emboli flow to the intracranial ves- lacunar stroke. Although second harmonic imaging has in-
sels in most cases and cause massive, superficial, single creased sensitivity of transthoracic echocardiography, con-
large striatocapsular or multiple infarcts in the middle cere- trast transesophageal echocardiography remains the standard
bral artery. Therefore, cardioembolic cerebral infarctions echocardiographic technique, particularly in young patients
predominate in the distribution territories of the carotid and with cryptogenic stroke. Transcranial Doppler (TCD) allows
the middle cerebral artery. Bilateral or multilevel posterior a first-line non-invasive diagnosis of right-to-left shunt
infarcts are suggestive of cardioembolism [23]. The presence caused by a patent foramen ovale by detecting bubble signs
of a potential major cardiac source of embolism in the ab- in the middle cerebral artery after the injection of agitated
sence of significant arterial disease remains the mainstay of saline in the antecubital vein. The most important limitation
clinical diagnosis of cardioembolic cerebral infarction [22]. of contrast TCD is the absence of a temporal bone window
When cardiac and arterial disease coexist (such as atrial fib- in 10% of patients who suffer stroke, a fact which particu-
rillation and ipsilateral carotid atheroma), determining the larly affects the older population. However, TCD does not
etiology of the ischemic stroke becomes more difficult.
Acute Cardioembolic Cerebral Infarction: Answers to Clinical Questions*
Adrià Arboixa,b* and Josefina Alióc
a
Cerebrovascular Division, Department of Neurology, Capio-Hospital Universitari del Sagrat Cor, Universitat de Bar-
celona, Barcelona, Spain; bCIBER de Enfermedades Respiratórias (CB06/06). Instituto Carlos III, Madrid; cDepartment
of Cardiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
Abstract: Cardioembolic cerebral infarction (CI) is the most severe subtype of ischaemic stroke but some clinical aspects
of this condition are still unclear. This article provides the reader with an overview and up-date of relevant aspects related
to clinical features, specific cardiac disorders and prognosis of CI. CI accounts for 1430% of ischemic strokes; patients
with CI are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate
treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of CI, including
sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke’s aphasia or global aphasia without
hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacu-
nar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely.
The most common disorders associated with a high risk of cardioembolism include atrial fibrillation, recent myocardial
infarction, mechanical prosthetic valve, dilated myocardiopathy and mitral rheumatic stenosis. Patent foramen ovale and
complex atheromatosis of the aortic arch are potentially emerging sources of cardioembolic infarction. Mitral annular cal-
cification can be a marker of complex aortic atheroma in stroke patients of unkown etiology. Transthoracic and trans-
esophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhyhtmia can be detected by Hol-
ter monitoring. Magnetic resonance imaging, transcranial Doppler, and electrophysiological studies are useful to docu-
ment the source of cardioembolism. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as
compared with other subtypes of cerebral infarction. Secondary prevention with anticoagulants should be started immedi-
ately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor
compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. Dabigatran has been shown to be non-inferior to
warfarin in the prevention of stroke or systemic embolism. All significant structural defects, such as atrial septal defects,
vegetations on valve or severe aortic disease should be treated. Aspirin is recommended in stroke patients with a patent
foramen ovale and indications of closure should be individualized. CI is an important topic in the frontier between cardiol-
ogy and vascular neurology, occurs frequently in daily practice, has a high impact for patients, and health care systems and
merits an update review of current clinical issues, advances and controversies.
Keywords: Cardioembolic stroke, recurrent embolization, atrial fibrillation, cardiac source of emboli, outcome, oral anticoagu-
lation, heart failure.
1. THE CLINICAL RELEVANCE OF CARDIOEM- In the Sagrat Cor Hospital of Barcelona Stroke Registry,
BOLIC CEREBRAL INFARCTION the frequency of cardioembolic stroke is 18% [14], a similar
percentage than that in the studies of Bougousslavsky et al.
Stroke is the leading cause of disability and the second
[15] (16%) and Timsit et al. [16] (19.4%), higher than that
most common cause of death worldwide [1-3]. Accurate
reported by Vázquez et al. [17] (14%) and de Al-Rajed et al.
definition of the mechanism of stroke is crucial as this will [18] (14%), but lower than the percentages of Rothrock et al.
guide the most effective care and therapy. Cardioembolic
[19] (22%) and Norrving and Löwenhielm [20] (30.6%).
cerebral infarction accounts approximately for one quarter of
However, the incidence of cardioembolic cerebral infarction
all cerebral infarcts [4-8]. In most cases, recurrence of cardi-
increases with age [14]. In the subgroup of patients younger
oembolism can be prevented by oral anticoagulants. There-
than 65 years of age, cardioembolic cerebral infarction oc-
fore, for a patient with a cerebral infarct, early confirmation
curred in 14.6% of cases but in very old patients (age 85
of a diagnosis of cardioembolic cerebral infarction is ex- years) cardioembolic stroke reached 36% of cases and is the
tremely important in order to initiate anticoagulation therapy
most frequent ischaemic subtype (Table 1).
for an adequate secondary prevention [9-13].
Embolism from the heart to the brain results from one of
three mechanisms: blood stasis and thrombus formation in an
*Address correspondence to this author at the Cerebrovascular Division, enlarged (or affected by another structure alteration) left car-
Department of Neurology, Capio-Hospital Universitari del Sagrat Cor, diac chamber (e.g., left ventricular aneurysm); release of
Universitat de Barcelona, Viladomat 288, E-08029 Barcelona, Spain; material from an abnormal valvular surface (e.g., calcific
Tel: +34–93–4948940; Fax: +34–93–4948906; E-mail:
*This manuscript is an updated version of Arboix A, Alió J. Cardioembolic degeneration); and abnormal passage from the venous to the
stroke: clinical features, specific cardiac disorders and prognosis. Current arterial circulation (paradoxical embolism) [3]. Cardiac em-
Cardiol. Rev. 2010; 6: 150161. boli can be of any size, but those of arising from the cardiac
1573-403X/12 $58.00+.00 © 2012 Bentham Science Publishers
, Acute Cardioembolic Cerebral Infarction Current Cardiology Reviews, 2012, Vol. 8, No. 1 55
Table 1. Distribution of Cerebral Infarctions According to Age in the Sagrat Cor Hospital of Barcelona Stroke Registry
Subtype of cerebral Years of age
infarction < 65 65–74 (n=501) 75–84 85
(n = 1840) (n= 314) (n=722) (n=303)
Cardioembolic 46 (14.6) 100 (20) 213 (29.5) 109 (36)
Atherothrombotic 66 (21.0) 159 (31.7) 233 (32.3) 95 (31.4)
Lacunar 93 (29.6) 159 (31.7) 173 (24) 59 (19.5)
Unknown cause 61 (19.4) 69 (13.8) 81 (11.2) 37 (12.2)
Unusual cause 48 (15.3) 14 (2.8) 22 (3.0) 3 (1)
Percentages in parenthesis.
chambers are often large and hence especially likely to cause However, in many patients, history, physical examination,
severe stroke, disability and death. Cardioembolic cerebral and routine diagnostic tests (electrocardiogram and findings
infarction is the most severe ischaemic stroke subtype, with on neuroimaging studies) are sufficient to easily make the
high in-hospital mortality rate (6–27%) and a substantial diagnosis of most presumed cardiac emboligenic condition
number of patients with neurological dysfunction at the time (e.g., atrial fibrillation, recent myocardial infarction, heart
of hospital discharge; however, the risk of early embolic failure, prior rheumatic disease, splinter hemorrhages) [23].
recurrence varies between 1 and 10% [3,6,21,22] (Fig. 1). An important exception is paroxysmal atrial fibrillation,
which can be detected by 2448 hour Holter monitoring
immediately after stroke. However, 24-hour Holter may not
be sufficient for diagnosing paroxysmal atrial fibrillation and
there is evidence supporting the value of prolonged cardiac
monitoring. In a recent study of Gaillard et al. [24], tran-
stelephonic ECG monitoring increased detection rate of par-
oxysmal atrial fibrillation in stroke and TIA patients whose
24-hour Holter monitoring was unrevealing, especially if
they had frequent premature atrial ectopic beats, recent ante-
rior circulation infarct on MRI, or both. The implantation of
subcutaneous devices for up to 14 months of rhythm moni-
toring increases the detection of paroxysmal atrial fibrillation
[25]. Prolonged cardiac rhythm monitoring increases the
detection of paroxysmal atrial fibrillation.
Transthoracic echocardiogram can disclose structural
cardiopathies (dilated cardiomyopathies, mitral stenosis and
Fig. (1). Histopathological specimen showing a hemorrhagic cere- other structural ventricular diseases and intraventricular
bral infarction of a cardioembolic origin with signs of ventricular thrombus, vegetations or tumors) and enables measurement
displacement and brain herniation in the territory of the middle of the left atrial size and left ventricular systolic function
cerebral artery. [1,2,23]. Transesophageal echocardiogram is able to study
the aortic arch and ascending aorta, left atrium and left atrial
There is no gold standard for making the diagnosis of appendages, intra-arterial septum, pulmonary veins and
cardioembolic cerebral infarction. Neuroimaging findings valve vegetations [1-3,23]. Transesophageal echocardiogra-
that support cardioembolic stroke include simultaneous or phy is more likely to be helpful in young patients with
sequential strokes in different arterial territories. Owing to stroke, stroke of unknown cause and in patients with non-
their large size, cardiac emboli flow to the intracranial ves- lacunar stroke. Although second harmonic imaging has in-
sels in most cases and cause massive, superficial, single creased sensitivity of transthoracic echocardiography, con-
large striatocapsular or multiple infarcts in the middle cere- trast transesophageal echocardiography remains the standard
bral artery. Therefore, cardioembolic cerebral infarctions echocardiographic technique, particularly in young patients
predominate in the distribution territories of the carotid and with cryptogenic stroke. Transcranial Doppler (TCD) allows
the middle cerebral artery. Bilateral or multilevel posterior a first-line non-invasive diagnosis of right-to-left shunt
infarcts are suggestive of cardioembolism [23]. The presence caused by a patent foramen ovale by detecting bubble signs
of a potential major cardiac source of embolism in the ab- in the middle cerebral artery after the injection of agitated
sence of significant arterial disease remains the mainstay of saline in the antecubital vein. The most important limitation
clinical diagnosis of cardioembolic cerebral infarction [22]. of contrast TCD is the absence of a temporal bone window
When cardiac and arterial disease coexist (such as atrial fib- in 10% of patients who suffer stroke, a fact which particu-
rillation and ipsilateral carotid atheroma), determining the larly affects the older population. However, TCD does not
etiology of the ischemic stroke becomes more difficult.
