Stroke Prevention in Atrial Fibrillation and Other Major Cardiac Sources of Embolism
Section snippets
Cardiac embolism and stroke
Cardioembolic stroke accounts for 20% of all ischemic strokes [1], and its frequency has increased over time, likely reflecting improvement in cardiac imaging [2]. Cardioembolic stroke can be caused by different cardiac disorders, but occurs most commonly from atrial fibrillation in adults (50%) (Fig. 1) [2], [3], [4]. Other important causes include ventricular thrombus (20%), structural heart defects or tumors (15%) and valvular heart disease (15%) (Table 1) [4], [5], [6], [7]. Although the
Diagnostic approach to cardioembolic stroke
A systematic approach is fundamental to diagnose patients who have experienced cardioembolic stroke. For example, the clinical history may provide clues to a cardioembolic source. Patients may have a history of palpitations (eg, mitral valve disease, atrial fibrillation), episodic or sustained tachycardia (eg, arrhythmia or atrial fibrillation with rapid ventricular response), angina or dyspnea (eg, myocardial infarction or heart failure), or stroke symptoms after valsalva (eg, cough, sneeze,
Stroke prevention in atrial fibrillation
Systemic embolization is a potential complication of any form of atrial fibrillation, and it can occur in patients with acute atrial fibrillation lasting as little as 72 hours [12]. The forms of atrial fibrillation proposed by the American College of Cardiology/AHA/ European Society of Cardiology are as follows [32], [33]:
• Paroxysmal: self-terminating atrial fibrillation, in which episodes generally last less than 7 days and usually less than 24 hours; it may be recurrent
• Persistent: fails to
Antithrombotic strategies
Before the late 1980s, antithrombotic therapy for stroke prevention in atrial fibrillation was limited to those who had rheumatic heart disease or prosthetic heart valves [37]. Between 1989 and 2007, 29 randomized trials were published, evaluating the efficacy and safety of antithrombotic agents for stroke prevention in atrial fibrillation [47]. These studies included 28,044 patients.
Patent foramen ovale
Patent foramen ovale (PFO) is a flap-like defect in the interatrial septum (Fig. 5) and a common finding (25%) in the general population. In utero, PFO allows oxygenated blood from the mother to bypass the lungs and go directly into fetal systemic circulation (by way of the right to left atria pathway). At birth, the lungs expand from breathing air, which fills the lungs with deoxygenated blood that enters the right atrium, the right ventricle, and the lung capillary beds. Blood is oxygenated
Medical therapy
Studies investigating medical therapy for PFO are largely retrospective and do not show any advantage of warfarin over aspirin (see Table 3). Most of these studies, however, have been limited by insufficient power to compare aspirin with warfarin, nonrandomized treatment allocation or nonmasked treatment, or allocation, crossover, or unblinded ascertainment of end points [6].
In the PFO in Cryptogenic Stroke Study (PICCS), patients were randomized to warfarin (international normalized ratio
Surgical and endovascular closure for patent foramen ovale
Recent methods to repair PFO using endovascular means have been developed within the past decade (Fig. 6) [67] and allow this anatomic defect to be treated less invasively [6], [67]. Given the association of PFO in cryptogenic stroke, repair of the defect is a logical target for subsequent stroke prevention. However, no randomized trial has been completed, despite five ongoing studies recruiting patients for PFO closure in cryptogenic stroke (www.clinicaltrials.gov identifiers, NCT00557479,
Aortic arch disease
An overlooked but a potentially serious source of embolic stroke is the aortic arch, especially when proximal aortic atheromatous disease is present [72]. Aortic embolic events may be misclassified as cryptogenic unless adequate transesophageal echocardiography of the aorta is performed. Aortic embolic disease manifests in different forms, including mobile and ulcerated plaques, aortic dissection, and aneurysms (Fig. 7). Patients who have ascending aorta or proximal arch plaques of 4 mm
Myocardial infarction, left ventricular dysfunction, and heart failure
Myocardial infarction, its associated ventricular wall immobility, and subsequent dilated cardiomyopathy may lead to left ventricular thrombus formation and cardioembolic stroke [76], [77], [78], [79], [80], [81]. Cardioembolic strokes may occur within 1 day of myocardial infarction, and approximately half occur within the first week, although stroke risk remains high up to 3 months and then decreases gradually [76], [77], [78], [79], [80], [81]. Anterior wall myocardial infarction carries a
Reduced left ventricular ejection fraction
Among patients older than 55 years, 3.9% have heart failure [83]. When heart failure occurs, stroke risk increases almost threefold by 5 years [84]. The Survival and Ventricular Enlargement (SAVE) trial [85] showed every decrease of five percentage points in left ventricular ejection fraction (LVEF) was accompanied by an 18% increase in stroke risk. More than 50 years ago, experts discovered that warfarin reduced the risk for pulmonary embolism, which was a major cause of death in patients who
Dilated cardiomyopathy
Dilated cardiomyopathy is associated with various different etiologies (ischemic and nonischemic, infectious and infiltrative). The Study of Left Ventricular Dysfunction (SOLVD) [92] clarified the relation between embolic stroke risk and worsening ventricular function. Increased stroke risk was seen only in women (2.4 events per 100 patient-years compared with 1.8 events per 100 patient-years in men). In this study, warfarin and aspirin were associated with a lower rate of death or
Aortic Stenosis
Clinically symptomatic cerebral embolic events are uncommon in calcific aortic valve disease (Fig. 8) [100], [101], [102], [103], [104] unless concomitant atrial fibrillation, reduced LVEF, or mitral valve disease is present. Calcific emboli to the retina (ie, asymptomatic emboli) or after valvuloplasty are reported [102], [105]. Antiplatelet therapy may be initiated in patients who have TIA and bicuspid calcific aortic stenosis, but anticoagulation is generally not recommended unless atrial
References (122)
- et al.
ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology
J Am Coll Cardiol
(2006) - et al.
Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators
J Am Coll Cardiol
(2000) Cardioembolic stroke: an update
Lancet Neurol
(2003)- et al.
ACCF/ASE/ACEP/ASNC/SCAI/SCCT/SCMR 2007 appropriateness criteria for transthoracic and transesophageal echocardiography: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American Society of Echocardiography, American College of Emergency Physicians, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance endorsed by the American College of Chest Physicians and the Society of Critical Care Medicine
J Am Coll Cardiol
(2007) - et al.
Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation
Am J Med
(2000) - et al.
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study
Lancet
(1989) - et al.
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study
J Am Coll Cardiol
(1991) - et al.
Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation
Am J Med
(2000) - et al.
Antithrombotic therapy in atrial fibrillation
Chest
(1998) - et al.
European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke
J Neurol Sci
(1996)
Alternate-day dosing of aspirin in atrial fibrillation. LASAF Pilot Study Group
Am Heart J
Primary prevention of arterial thromboembolism in the oldest old with atrial fibrillation - a randomized pilot trial comparing adjusted-dose and fixed low-dose coumadin with aspirin
Eur J Intern Med
Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study
J Am Coll Cardiol
Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest
Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque
Am J Cardiol
Mobile aortic atheroma and systemic emboli: efficacy of anticoagulation and influence of plaque morphology on recurrent stroke
J Am Coll Cardiol
Antithrombotic agents in coronary artery disease
Chest
Ischemic stroke after heart failure: a community-based study
Am Heart J
The effect of dicumarol upon the mortality and incidence of thromboembolic complications in congestive heart failure
Am Heart J
Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials
J Am Coll Cardiol
Anticoagulation in dilated cardiomyopathy
J Am Coll Cardiol
The natural history of idiopathic dilated cardiomyopathy
Am J Cardiol
The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics
J Card Fail
Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design
J Card Fail
Cardiogenic brain embolism: the second report of Cerebral Embolism Task Force
Arch Neurol
Cardiac sources of embolism and crebral infarction–clinical consequences and vascular concomitants: the Lausanne Stroke Registry
Neurology
Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation
JAMA
Patent foramen ovale and cryptogenic stroke in older patients
N Engl J Med
Clinical practice. Patent foramen ovale in young adults with unexplained stroke
N Engl J Med
Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both
N Engl J Med
Evaluating cardiac sources of embolic stroke with MRI
Echocardiography
Mechanisms in lacunar infarction
Stroke
Sensorimotor stroke; clinical features, MRI findings, and cardiac and vascular concomitants in 32 patients
Acta Neurol Scand
‘Spectacular shrinking deficit’: rapid recovery from a major hemispheric syndrome by migration of an embolus
Neurology
Intracranial branch atheromatous disease: a neglected, understudied, and underused concept
Neurology
Can embolic stroke be diagnosed on the basis of neurologic clinical criteria?
Arch Neurol
Cerebral embolism in the Michael Reese Stroke Registry
Stroke
Early differentiation of cardioembolic from atherothrombotic cerebral infarction: a multivariate analysis
Eur J Neurol
Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists
Circulation
Therapeutic strategies after examination by transesophageal echocardiography in 503 patients with ischemic stroke
Stroke
Incidence of transcranial Doppler-detected cerebral microemboli in patients referred for echocardiography
Stroke
Posterior circulation ischemia: then, now, and tomorrow. The Thomas Willis Lecture-2000
Stroke
The etiology of posterior circulation infarcts: a prospective study using magnetic resonance imaging and magnetic resonance angiography
Neurology
New England Medical Center Posterior Circulation registry
Ann Neurol
Outcome at 30 days in the New England Medical Center Posterior Circulation Registry
Arch Neurol
The Basilar Artery International Cooperative Study (BASICS)
Int J Stroke
Clinical features and mechanism of occipital infarction
Ann Neurol
Posterior cerebral artery territory infarcts in the New England Medical Center Posterior Circulation Registry
Arch Neurol
Electron beam computed tomography for the detection of left atrial thrombi in patients with atrial fibrillation
Heart
Cited by (21)
Cardiac Diseases
2021, Stroke: Pathophysiology, Diagnosis, and ManagementInfluence of oral anticoagulation on stroke severity and outcomes: A propensity score matching case-control study
2020, Journal of the Neurological SciencesCitation Excerpt :Cardioembolism is one of the most frequent causes of ischemic stroke (IS), accounting for 20% of all IS [1].
Retrochiasmal Disorders
2018, Liu, Volpe, and Galetta's Neuro-Ophthalmology: Diagnosis and ManagementNew anticoagulants (dabigatran, apixaban, rivaroxaban) for stroke prevention in atrial fibrillation
2013, Neurologic ClinicsCitation Excerpt :The most common source of cardiac embolism in adults is atrial fibrillation (AF).1 Evidence supports the use of antithrombotic therapy for most patients who have AF; oral anticoagulants are more effective but also carry higher risk of hemorrhagic complications than antiplatelet agents.2 For more than 5 decades, warfarin has been the only oral agent available for chronic outpatient management of AF.
Temporal relationship of atrial tachyarrhythmias, cerebrovascular events, and systemic emboli based on stored device data: A subgroup analysis of TRENDS
2011, Heart RhythmCitation Excerpt :A final result is the corollary finding that 11 (27%) of 40 patients had AT/AF within 30 days of CVE/SE. This finding implies a causal effect of AF and CVE/SE, with a rate similar to that reported in other studies.1–4,11 The results of the current study suggest that CVE/SE is likely due to multiple mechanisms.
Neurological Malpractice and Nonmalpractice Liability
2010, Neurologic ClinicsCitation Excerpt :Nonvalvular atrial fibrillation affects 2.5 million Americans and the prevalence increases with age; it increases the risk of stroke fourfold to sixfold across all age groups.47,48 The annual rate of ischemic stroke in untreated nonvalvular atrial fibrillation patients increases with high-risk factors, such as hypertension, left ventricular dysfunction, transient ischemic attack (TIA), or prior stroke.49 Anticoagulation with warfarin significantly reduces this risk of stroke, and represents the generally accepted standard of care for stroke prevention in these patients.50
Dr. Freeman acknowledges research funding provided in part by the Robert H. and Clarice Smith/M.L. Simpson Foundation Trust. Dr. Aguilar chairs the Event Adjudication Committee for the NINDS-sponsored SPS3 trial.