| Current
Cardiology Reviews
ISSN: 1573-403X
Current Cardiology Reviews
Volume 6, Number 3, August 2010
Contents
Cardioembolic Infarction: A Renewed Topic of Interest
Guest Editor: Adrià Arboix
Editorial Pp. 137
Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic
Heart Diseases: Similarities and Differences Pp.
138-149
Ernest Palomeras Soler and Virgina Casado Ruiz
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Cardioembolic Stroke: Clinical Features, Specific
Cardiac Disorders and Prognosis Pp. 150-161
Adrià Arboix and Josefina Alió
[Abstract] [Purchase
Article]
Patent Foramen Ovale in Cerebral Infarction
Pp. 162-174
Joaquin Serena, María Jiménez-Nieto, Yolanda
Silva and Mar Castellanos
[Abstract] [Purchase
Article]
Cardiac Workup of Ischemic Stroke Pp.
175-183
Xavier Ustrell and Anna Pellisé
[Abstract] [Purchase
Article]
Complex Atheromatosis of the Aortic Arch in Cerebral
Infarction Pp. 184-193
Ramón Pujadas Capmany, Montserrat Oliveras Ibañez
and Xavier Jané Pesquer
[Abstract] [Purchase
Article]
Blood Biomarkers in Cardioembolic Stroke
Pp. 194-201
Teresa García-Berrocoso, Israel Fernández-Cadenas,
Pilar Delgado, Anna Rosell and Joan Montaner
[Abstract] [Purchase
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Heart Failure in Acute Ischemic Stroke
Pp. 202-213
Elisa Cuadrado-Godia, Angel Ois and Jaume Roquer
[Abstract] [Purchase
Article]
Cerebrovascular Complications After Heart Transplantation
Pp. 214-217
Aída Alejaldre, Raquel Delgado-Mederos, Miguel
Ángel Santos and Joan Martí-Fàbregas
[Abstract] [Purchase
Article]
Fibrinolytic Therapy in Acute Stroke
Pp. 217-226
Mònica Millán, Laura Dorado and
Antoni Dávalos
[Abstract] [Purchase
Article]
Antithrombotic Therapy in Cardiac Embolism
Pp. 227-237
Álvaro Cervera and Ángel Chamorro
[Abstract] [Purchase
Article]
Angiogenesis, Neurogenesis and Neuroplasticity
in Ischemic Stroke Pp. 238-244
M. Angels Font Padros, Adriá Arboix and
Jerzy Krupinski
[Abstract] [Purchase
Article]
Abstracts
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Editorial: Cardioembolic Infarction: A Renewed Topic
of Interest
Cardioembolic infarction accounts for one quarter
of all cerebral infarcts and is the most severe subtype of
ischemic stroke. The rate of in-hospital death may be as high
as 27% and a few patients are symptom-free at discharge from
the hospital. Major cardiac sources of embolism are well-established
and cardioembolic stroke is largely preventable. However,
once stroke due to cardiac embolism has occurred, the likelihood
of recurrence is relatively high (up to 10% for early embolic
recurrence). Therefore, efforts at primary prevention for
major-risk cardioembolic sources and secondary prevention
of recurrence are very important. Although large series of
patients with cardioembolic infarction have been reported
in the literature, some clinical aspects of the natural course
of the disease are still poorly defined.
The objective of this supplement is to present an update review
of relevant aspects related to clinical manifestations, biological
characteristics, prognostic implications and treatment of
cardioembolic stroke, in order to contribute to improve the
quality of care and outcome of acute stroke patients. The
most relevant aspects of cardioembolic infarction are discussed
in the following 11 chapters: 1)epidemiology and risk factors
of cerebral ischemia and ischemic heart diseases: similarities
and differences; 2) clinical and prognostic features of cardioembolic
stroke; 3) patent oval foramen in cerebral infarction; 4)
cardiac workup of ischemic stroke; 5) complex atheromatosis
of the aortic arch in cerebral infarction; 6) blood biomarkers
in cardioembolic stroke; 7) heart failure in acute ischemic
stroke; 8) cerebrovascular disease as a complication of cardiac
transplantation; 9) antithrombotic therapy in cardiac embolism;
10) thrombolytic therapy in acute stroke; and 11) angiogenesis,
neurogenesis and neuroplasticity in ischemic stroke.
Cerebral cardioembolism is an important topic in the frontier
between cardiology and vascular neurology, occurs frequently
in daily practice, and has a high impact for patients, health
care systems and society. It is for all these reasons that
an update on cardioembolic infarction is now fully justified.
It is worth mentioning that a team of excellent professionals
belonging to the Expert Committee on Cerebrovascular Diseases
of the Catalonian Society of Neurology and with proven experience
in the field have contributed to the different chapters. My
gratitude to all contributors for their support of this project
and particularly to Dr. Jianyi Zhang, Editor-in-Chief of the
Current Cardiology Reviews series. We hope that clinicians
involved in the care of patients with cardioembolic infarction
and interested in this topic will profit this publication
and find this resource valuable and useful.
Adrià Arboix, MD
Cerebrovascular Division
Department of Neurology
Hospital Universitari del Sagrat Cor
Universitat de Barcelona
Viladomat 288
E-08029 Barcelona
Spain
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Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic
Heart Diseases: Similarities and Differences
Ernest Palomeras Soler and Virgina Casado Ruiz
Cerebral ischemia and ischemic heart diseases, common
entities nowadays, are the main manifestation of circulatory
diseases. Cardiovascular diseases, followed by stroke, represent
the leading cause of mortality worldwide. Both entities share
risk factors, pathophisiology and etiologic aspects by means
of a main common mechanism, atherosclerosis. However, each
entity has its own particularities. Ischemic stroke shows
a variety of pathogenic mechanisms not present in ischemic
heart disease. An ischemic stroke increases the risk of suffering
a coronary heart disease, and viceversa. The aim of this chapter
is to review data on epidemiology, pathophisiology and risk
factors for both entities, considering the differences and
similarities that could be found in between them. We discuss
traditional risk factors, obtained from epidemiological data,
and also some novel ones, such as hyperhomocisteinemia or
sleep apnea. We separate risk factors, as clasically, in two
groups: nonmodifiables, which includes age, sex, or ethnicity,
and modifiables, including hypertension, dyslipidemia or diabetis,
in order to discuss the role of each factor in both ischemic
events, ischemic stroke and coronary heart disease.
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Cardioembolic Stroke: Clinical Features, Specific
Cardiac Disorders and Prognosis
Adrià Arboix and Josefina Alió
This article provides the reader with an overview and
up-date of clinical features, specific cardiac disorders and
prognosis of cardioembolic stroke. Cardioembolic stroke accounts
for 14-30% of ischemic strokes and, in general, is a severe
condition; patients with cardioembolic infarction 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 cardioembolic infarction, 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. Lacunar
clinical presentations, a lacunar infarct and especially multiple
lacunar infarcts, make cardioembolic origin unlikely. The
more common high risk cardioembolic conditions are atrial
fibrillation, recent myocardial infarction, mechanical prosthetic
valve, dilated myocardiopathy, and mitral rheumatic stenosis.
Transthoracic and transesophageal echocardiogram can disclose
structural heart diseases. Paroxysmal atrial dysrhyhtmia can
be detected by Holter monitoring. In-hospital mortality in
cardioembolic stroke (27.3%, in our series) is the highest
as compared with other subtypes of cerebral infarction. In
our experience, in-hospital mortality in patients with early
embolic recurrence (within the first 7 days) was 77%. Patients
with alcohol abuse, hypertension, valvular heart disease,
nausea and vomiting, and previous cerebral infarction are
at increased risk of early recurrent systemic embolization.
Secondary prevention with anticoagulants should be started
immediately 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.
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Patent Foramen Ovale in Cerebral Infarction
Joaquin Serena, María Jiménez-Nieto, Yolanda
Silva and Mar Castellanos
Recent studies support the hypothesis of a close aetiological
and pathogenic association between the presence of patent
foramen ovale (PFO) and cryptogenic stroke. The therapeutic
options currently used in the treatment of these patients
range from standard antiaggregation and standard-dose anticoagulation
to the percutaneous occlusion of the PFO. The use or recommendation
of treatment is based both on clinical risk factors associated
with PFO, such as age, detection of states of hypercoagulability
and previous history of stroke, and on the risks associated
to right-to-left shunt (RLSh) and PFO, such as the size of
PFO, magnitude of RLSh and the presence of atrial septal aneurysm
(ASA). However, there is currently no consensus regarding
the most suitable treatment and it is surprising to observe
the widespread use of certain therapeutic approaches which
are not supported by clinical evidence.
In this revision, we analyse the relevance of PFO in cryptogenic
stroke, consider the main evidence available for determining
the best management of these patients and make diagnostic
and therapeutic management recommendations.
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Cardiac Workup of Ischemic Stroke
Xavier Ustrell and Anna Pellisé
Stroke is the leading cause of disability in developed
countries and the third cause of mortality. Up to 15-30% of
ischemic strokes are caused by cardiac sources of emboli being
associated with poor prognosis and high index of fatal recurrence.
In order to establish an adequate preventive strategy it is
crucial to identify the cause of the embolism. After a complete
diagnostic workup up to 30% of strokes remain with an undetermined
cause, and most of them are attributed to an embolic mechanism
suggesting a cardiac origin.
There is no consensus in the extent and optimal approach of
cardiac workup of ischemic stroke. Clinical features along
with brain imaging and the study of the cerebral vessels with
ultrasonography or MRI/CT based angiography can identify other
causes or lead to think about a possible cardioembolic origin.
Atrial fibrillation is the most common cause of cardioembolic
stroke. Identification of occult atrial fibrillation is essential.
Baseline ECG, serial ECG(’s), cardiac monitoring during
the first 48 hours, and Holter monitoring have detection rates
varying from 4 to 8% each separately. Extended cardiac monitoring
with event loop recorders has shown higher rates of detection
of paroxysmal atrial fibrillation.
Cardiac imaging with echocardiography is necessary to identify
structural sources of emboli. There is insufficient data to
determine which is the optimal approach. Transthoracic echocardiography
has an acceptable diagnostic yield in patients with heart
disease but transesophageal echocardiography has a higher
diagnostic yield and is necessary if no cardiac sources have
been identified in patients with cryptogenic stroke with embolic
mechanism.
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Complex Atheromatosis of the Aortic Arch in Cerebral
Infarction
Ramón Pujadas Capmany, Montserrat Oliveras Ibañez
and Xavier Jané Pesquer
In many stroke patients it is not possible to establish
the etiology of stroke. However, in the last two decades,
the use of transesophageal echocardiography in patients with
stroke of uncertain etiology reveals atherosclerotic plaques
in the aortic arch, which often protrude into the lumen and
have mobile components in a high percentage of cases. Several
autopsy series and retrospective studies of cases and controls
have shown an association between aortic arch atheroma and
arterial embolism, which was later confirmed by prospectively
designed studies. The association with ischemic stroke was
particularly strong when atheromas were located proximal to
the ostium of the left subclavian artery, when the plaque
was ≥
4 mm thick and particularly when mobile components are present.
In these cases, aspirin might not prevent adequately new arterial
ischemic events especially stroke. Here we review the evidence
of aortic arch atheroma as an independent risk factor for
stroke and arterial embolism, including clinical and pathological
data on atherosclerosis of the thoracic aorta as an embolic
source. In addition, the impact of complex plaques (≥
4 mm thick, or with mobile components) on increasing the risk
of stroke is also reviewed. In non-randomized retrospective
studies anticoagulation was superior to antiplatelet therapy
in patients with stroke and aortic arch plaques with mobile
components. In a retrospective case-control study, statins
significantly reduced the relative risk of new vascular events.
However, given the limited data available and its retrospective
nature, randomized prospective studies are needed to establish
the optimal secondary prevention therapeutic regimens in these
high risk patients.
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Blood Biomarkers in Cardioembolic Stroke
Teresa García-Berrocoso, Israel Fernández-Cadenas,
Pilar Delgado, Anna Rosell and Joan Montaner
One promising field in neurovascular diseases investigation
is the use of biomarkers to guide stroke etiology diagnosis
and classification. Since treatment differs among etiologic
subtypes and nowadays many patients receive a diagnosis of
undetermined stroke, biomarkers might become an important
additional diagnostic tool. In this review we update current
knowledge about biomarkers related with cardioembolic stroke
etiology (such as BNP and D-dimer proteins, or PITX2
and ZFHX3 genes), that in the future, might allow
rapidly guiding other diagnostic tests and accelerating the
onset of an optimal secondary prevention.
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Heart Failure in Acute Ischemic Stroke
Elisa Cuadrado-Godia, Angel Ois and Jaume Roquer
Heart failure (HF) is a complex clinical syndrome that
can result from any structural or functional cardiac disorder
that impairs the ability of the ventricle to fill with or
eject blood. Due to the aging of the population it has become
a growing public health problem in recent decades. Diagnosis
of HF is clinical and there is no diagnostic test, although
some basic complementary testing should be performed in all
patients. Depending on the ejection fraction (EF), the syndrome
is classified as HF with low EF or HF with normal EF (HFNEF).
Although prognosis in HF is poor, HFNEF seems to be more benign.
HF and ischemic stroke (IS) share vascular risk factors such
as age, hypertension, diabetes mellitus, coronary artery disease
and atrial fibrillation. Persons with HF have higher incidence
of IS, varying from 1.7% to 10.4% per year across various
cohort studies. The stroke rate increases with length of follow-up.
Reduced EF, independent of severity, is associated with higher
risk of stroke. Left ventricular mass and geometry are also
related with stroke incidence, with concentric hypertrophy
carrying the greatest risk.
In HF with low EF, the stroke mechanism may be embolism, cerebral
hypoperfusion or both, whereas in HFNEF the mechanism is more
typically associated with chronic endothelial damage of the
small vessels. Stroke in patients with HF is more severe and
is associated with a higher rate of recurrence, dependency,
and short term and long term mortality. Cardiac morbidity
and mortality is also high in these patients. Acute stroke
treatment in HF includes all the current therapeutic options
to more carefully control blood pressure. For secondary prevention,
optimal control of all vascular risk factors is essential.
Antithrombotic therapy is mandatory, although the choice of
a platelet inhibitor or anticoagulant drug depends on the
cardiac disease. Trials are ongoing to evaluate anticoagulant
therapy for prevention of embolism in patients with low EF
who are at sinus rhythm.
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Cerebrovascular Complications After Heart Transplantation
Aída Alejaldre, Raquel Delgado-Mederos, Miguel
Ángel Santos and Joan Martí-Fàbregas
Neurological complications in orthotopic heart transplantation
represent a major cause of morbidity and mortality despite
successful transplantation. The most frequent perioperative
neurological complications are delirium or encephalopathy.
In this period cerebrovascular complication ranges between
5-11%. After the perioperative period, the 5-year stroke risk
after cardiac transplantation is 4.1%. In a retrospective
study conducted with 314 patients who underwent cardiac transplantation,
it was found that 20% of cerebrovascular complications occurred
within the first two weeks after transplantation, while 80%
occurred in the late postoperative phase. Of these, ischemic
stroke is the most common subtype.
In the perioperative periode, hemodynamic instability, cardiac
arrest, extracorporeal circulation over 2 hours, prior history
of stroke, and carotid stenosis greater than 50% have been
reported to be risk factors for the occurrence of cerebrovascular
complications. Perioperative cerebrovascular complications
are associated with higher mortality and poor functional outcome
at one year follow-up.
After the perioperative period, the only factor that has been
significantly associated with an increased risk of cerebrovascular
complications is a history of prior stroke, either ischemic
or hemorrhagic. Other associated factors include unknown atrial
fibrillation, septic emboli from endocarditis, cardiac catheterization
and perioperative hemodynamic shock. According to the TOAST
etiologic classification, the most prevalent etiologic subtype
of ischemic stroke is undetermined cause.
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Fibrinolytic Therapy in Acute Stroke
Mònica Millán, Laura Dorado and
Antoni Dávalos
Acute ischemic stroke is a major cause of morbidity and
mortality in Europe, North America, and Asia. Its treatment
has completely changed over the past decade with different
interventional approaches, such as intravenous trials, intra-arterial
trials, combined intravenous/intra-arterial trials, and newer
devices to mechanically remove the clot from intracranial
arteries. Intravenous thrombolysis with tissue plaminogen
activator (tPA) within 4.5 hours of symptoms onset significantly
improved clinical outcomes in patients with acute ischemic
stroke. Pharmacological intra-arterial thrombolysis has been
shown effective until 6 hours after middle cerebral artery
occlusion and offers a higher rate of recanalization compared
with intravenous thrombolysis, whereas combined intravenous/
intra-arterial thrombolysis seems to be as safe as isolated
intravenous thrombolysis. The more recent advances in reperfusion
therapies have been done in mechanical embolus disruption
or removal. Merci Retriever and Penumbra System have been
approved for clot removal in brain arteries, but not as a
therapeutic modality for acute ischemic stroke since it is
no clear whether mechanical thrombectomy improves clinical
outcome in acute stroke. However, mechanical devices are being
used in clinical practice for patients who are ineligible
for tPA or who have failed to respond to intravenous tPA.
We summarize the results of the major thrombolytic trials
and the latest neurointerventional approaches to ischemic
stroke.
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Antithrombotic Therapy in Cardiac Embolism
Álvaro Cervera and Ángel Chamorro
Anticoagulation is indicated in most cardioembolic ischemic
strokes for secondary prevention. In many cardiac conditions,
anticoagulation is also indication for primary stroke prevention,
mainly when associated to vascular risk factors. Anticoagulation
should be started as soon as possible, as it is safe even
in moderate acute strokes. The efficacy of early anticoagulation
after cardioembolic stroke in relation to outcome has not
been assessed adequately, but there is evidence from animal
models and clinical studies that anticoagulation with unfractionated
heparin is associated with a better outcome mediated in part
by its anti-inflammatory properties.
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Angiogenesis, Neurogenesis and Neuroplasticity
in Ischemic Stroke
M. Angels Font Padros, Adriá Arboix and
Jerzy Krupinski
Only very little is know about the neurovascular niche
after cardioembolic stroke. Three processes implicated in
neurorepair: angiogenesis, neurogenesis and synaptic plasticity,
would be naturally produced in adult brains, but also could
be stimulated through endogen neurorepair phenomena. Angiogenesis
stimulation generates new vessels with the aim to increase
collateral circulation. Neurogenesis is controlled by intrinsic
genetic mechanisms and growth factors but also ambiental factors
are important. The leading process of the migrating neural
progenitor cells (NPCs) is closely associated with blood vessels,
suggesting that this interaction provides directional guidance
to the NPCs. These findings suggest that blood vessels play
an important role as a scaffold for NPCs migration toward
the damaged brain region. DNA microarray technology and blood
genomic profiling in human stroke provided tools to investigate
the expression of thousands of genes. Critical comparison
of gene expression profiles after stroke in humans with those
in animal models should lead to a better understanding of
the pathophysiology of brain ischaemia. Probably the most
important part of early recovery after stroke is limited capacity
of penumbra/infarct neurones to recover. It became more clear
in the last years, that penumbra is not just passively dying
over time but it is also actively recovering. This initial
plasticity in majority contributes towards later neurogenesis,
angiogenesis and final recovery. Penumbra is a principal target
in acute phase of stroke. Thus, the origin of newly formed
vessels and the pathogenic role of neovascularization and
neurogenesis are important unresolved issues in our understanding
of the mechanisms after stroke. Biomaterials for promoting
brain protection, repair and regeneration are new hot target.
Recently developed biomaterials can enable and increase the
target delivery of drugs or therapeutic proteins to the brain,
allow cell or tissue transplants to be effectively delivered
to the brain and help to rebuild damaged circuits. These new
approaches are gaining clear importance because nanotechnology
allows better control over material-cell interactions that
induce specific developmental processes and cellular responses
including differentiation, migration and outgrowth.
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