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Vol. 64. Issue 4.
Pages 319-327 (April 2011)
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Vol. 64. Issue 4.
Pages 319-327 (April 2011)
DOI: 10.1016/j.rec.2010.12.010
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Neurology and Cardiology: Points of Contact
Neurología y cardiología: puntos de contacto
Larry B. Goldsteina,
, Nada El Husseinia
a Division of Neurology, Department of Medicine, Duke Stroke Center, Duke University Medical Center, Durham, North Carolina, United States
b Durham VA Medical Center, Durham, North Carolina, United States
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Los ictus debidos a enfermedades cardiacas y las anomalías cardiacas asociadas a trastornos neuromusculares son ejemplos de los muchos puntos de contacto entre la neurología y la cardiología. Aproximadamente un 20-30% de los ictus están relacionados con enfermedades cardiacas como fibrilación auricular, insuficiencia cardiaca congestiva, endocarditis bacteriana, valvulopatías reumáticas y no reumáticas, infarto agudo de miocardio con trombo ventricular izquierdo y miocardiopatías asociadas a distrofias musculares, entre otras. Los ictus pueden producirse también en el contexto de intervenciones cardiacas, como un cateterismo o una operación de bypass arterial coronario. El tratamiento para la prevención de la recurrencia del ictus en cualquiera de estos contextos depende de la etiología subyacente. Mientras que se ha demostrado que la anticoagulación con antagonistas de la vitamina K es superior al empleo de ácido acetilsalicílico para la prevención del ictus en la fibrilación auricular, la superioridad de los anticoagulantes no se ha establecido de manera concluyente en los ictus asociados a insuficiencia cardiaca congestiva y su uso está contraindicado en los casos de endocarditis infecciosa. En ensayos actualmente en curso, se están evaluando estrategias de tratamiento en pacientes con cortocircuitos auriculares debidos a un foramen oval permeable. Las miocardiopatías y las anomalías de la conducción forman parte del espectro de muchos trastornos neuromusculares, incluidos los trastornos mitocondriales y las distrofias musculares. Cardiólogos y neurólogos comparten la responsabilidad de la asistencia de los pacientes con ictus cardiogénicos o con riesgo de sufrirlos, así como de la detección y el manejo de la cardiopatía asociada a los trastornos neuromusculares.

Palabras clave:

Strokes resulting from cardiac diseases, and cardiac abnormalities associated with neuromuscular disorders are examples of the many points of contact between neurology and cardiology. Approximately 20%-30% of strokes are related to cardiac diseases, including atrial fibrillation, congestive heart failure, bacterial endocarditis, rheumatic and nonrheumatic valvular diseases, acute myocardial infarction with left ventricular thrombus, and cardiomyopathies associated with muscular dystrophies, among others. Strokes can also occur in the setting of cardiac interventions such as cardiac catheterization and coronary artery bypass procedures. Treatment to prevent recurrent stroke in any of these settings depends on the underlying etiology. Whereas anticoagulation with vitamin K antagonists is proven to be superior to acetylsalicylic acid for stroke prevention in atrial fibrillation, the superiority of anticoagulants has not been conclusively established for stroke associated with congestive heart failure and is contraindicated in those with infective endocarditis. Ongoing trials are evaluating management strategies in patients with atrial level shunts due to patent foramen ovale. Cardiomyopathies and conduction abnormalities are part of the spectrum of many neuromuscular disorders including mitochondrial disorders and muscular dystrophies. Cardiologists and neurologists share responsibility for caring for patients with or at risk for cardiogenic strokes, and for screening and managing the heart disease associated with neuromuscular disorders.

Full Text

Neurologists and cardiologists are frequently involved in coordinating the care of patients with a variety of conditions, the most common being stroke. This article reviews the diagnosis and management of conditions that have both cardiac and neurologic manifestations. The review is organized by cardiac disorders that predispose to neurological complications and neurological conditions that can involve the heart.

Neurological complications of cardiac disease

Cardiac diseases can be complicated by stroke, cognitive impairment, and brain infections. Cardiac conditions including atrial fibrillation (AF), cardiomyopathies, valvular heart disease and interatrial septal anomalies account for 20%-30% of all ischemic strokes.1,2 The mechanism of cardiogenic stroke is often embolic, but hypoperfusion may also occur, particularly in those with cerebral steno-occlusive disease. Cognitive decline can be associated with congestive heart failure (CHF) and coronary artery bypass graft procedures, whereas meningitis and brain abscesses are possible complications of infective endocarditis (IE).

Atrial Fibrillation

Nonvalvular AF is the most common cause of cardiogenic stroke, accounting for 50% of cardiogenic emboli and 10% of ischemic strokes.1,2 It affects about 1% of the general population and is the most common cardiac arrhythmia in the elderly, having a prevalence of nearly 10% in those older than 80years.1,2 AF is associated with a 4- to 5-fold increased risk of stroke across all age groups; those who also had a prior stroke or transient ischemic attack (TIA) have an additional 2.5-fold increase in stroke risk.1,2 Depending on comorbidities, the incidence of stroke among non-anticoagulated patients with AF ranges between 4.5% and 13% per year.1

Both persistent and paroxysmal AF increase the risk of first and recurrent stroke.2,3 AF explains up to about a quarter of cryptogenic strokes in some series. Cardiac monitoring to detect paroxysmal AF in stroke patients is cost effective across a wide range of factors.4,5

Heart failure, hypertension, increasing age, diabetes, prior thromboembolism including prior strokes, left ventricular dysfunction, left atrial enlargement, mitral annular calcification, spontaneous echo contrast, and left atrial thrombus increase stroke risks in those with AF.2 The predictive capacity of stroke risk stratification schemes in patients with nonvalvular AF vary greatly.6 The CHADS2 score is among the most commonly used schemes; it assigns 1 point for CHF, hypertension, age over 75years, diabetes mellitus, and 2 points for a history of stroke or TIA.7 Each point increase in the CHADS2 score increases the stroke risk by a factor of 1.5 (95% confidence interval [CI], 1.3-1.7); the stroke rate per 100 patient-years is 1.9 (95% CI, 1.2-3.0) for a score of 0 and 18.2 (95% CI, 10.5-27.4) for a score of 6.7

Multiple clinical trials have established the benefit of warfarin in patients with nonvalvular AF. Warfarin was compared to placebo in 5 primary prevention trials.8,9,10,11,12 Two of these also compared acetylsalicylic acid to placebo.12 Pooled data from these 5 trials reflect a 68% risk reduction with warfarin (95% CI, 50% to 79%) and a 36% reduction (95% CI, 4% to 57%) with acetylsalicylic acid.13 Warfarin treatment results in 3.1% (p<0.001) absolute annual stroke risk reduction: 31 ischemic strokes are prevented for every 1000 patients treated.2,13 An international normalized ratio [INR] between 2.0 and 3.0 is recommended for preventing strokes while minimizing the risk of hemorrhage.14,15

Warfarin, however, remains underutilized in patients with AF because of its narrow therapeutic index and its numerous food and drug interactions that necessitate frequent INR monitoring.2 Alternative strategies have included the use of antiplatelet drugs, direct thrombin inhibitors and factor Xa antagonists. Warfarin was superior to acetylsalicylic acid (300 mg) in the secondary prevention of stroke/TIA in the European Atrial Fibrillation Trial (EAFT); hazard ratio (HR) for the combination of vascular death, any stroke, myocardial infarction (MI) and systemic embolism 0.60, (95% CI, 0.41-0.87).16 Warfarin was also superior to acetylsalicylic acid in elderly patients with nonvalvular AF enrolled in the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study. The relative risk (RR) for stroke was 0.48 (95% CI, 0.28-0.80) in favor of warfarin, with no significant difference in the rate of hemorrhage.17 The American Heart Association (AHA)/American Stroke Association recommends acetylsalicylic acid for those with AF who are unable to take oral anticoagulant.2 High risk patients who take an anticoagulant and stop it temporarily are at high risk for strokes. Bridging with a low molecular weight heparin administered subcutaneously is deemed to be reasonable in this setting.2

The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W) study found that warfarin was superior to the combination of clopidogrel plus acetylsalicylic acid for the prevention of vascular events.18 For patients for whom a vitamin K antagonist was deemed “unsuitable,” ACTIVE W found that the combination of clopidogrel and acetylsalicylic acid was superior to acetylsalicylic acid alone in preventing vascular events (RR = 0.89; 95% CI, 0.81-0.98; p=0.01) but carried a higher risk of major bleeding (RR=1.57; 95% CI, 1.29-1.92).19,20

Ximelagatran and dabigatran are direct thrombin inhibitors that were compared to warfarin in patients with AF. Ximelagatran was not inferior to warfarin with a comparable bleeding risk in two randomized controlled trials (SPORTIF III and SPORTIF V), but caused clinically significant hepatotoxicity.21,22 Depending on dose, patients randomized to dabigatran had rates of stroke and systemic embolism similar to those taking warfarin, with lower rates of major hemorrhage.23 Dabigatran was recently approved by the United States Food and Drug Administration as an alternative to warfarin in patients with AF. Dabigatran may interact with other drugs, such as P-glycoprotein inducers.

Rivaroxaban (ROCKET AF study) and Apixaban (ARISTOTLE trial) are oral factor Xa inhibitors. Initial reports indicate that this class of drug may be a viable alternative to warfarin in patients with AF.20,24 The anticoagulant effects of direct thrombin inhibitors and factor Xa inhibitors are not immediately reversible. Whether patients who receive these drugs can be treated with intravenous thrombolytics if they were to have a stroke is unknown.

Patent Foramen Ovale/Atrial Septal Aneurysm

A causal relationship between patent foramen ovale (PFO) and cryptogenic stroke remains uncertain. Approximately 25% of the general population has a PFO.25 Patients with a PFO may also have an atrial septal aneurysm (ASA), defined as >10mm septal excursion with a base of 1.5cm or greater.2,26 Potential mechanisms of stroke in patients with PFO with or without an ASA include: a) paradoxical embolization; b) embolization of thrombus from the rim of the ASA; c) paroxysmal AF related to damage to the cardiac conduction system; d) passage of unmeasured vasoactive humoral substances that escape pulmonary degradation; and/or e) causes not related to the defect.27,28 A potential source of paradoxical embolization is identified in 10% to 57% of patients with PFO and cryptogenic strokes.27,29

A meta-analysis of case-control studies established a higher prevalence of PFO and ASA in stroke patients overall and in those who had cryptogenic strokes.26 The combination was more frequent in those with stroke compared to nonstroke control subjects (odds ratio [OR] =5.25; 95% CI, 2.91-9.45), in those with cryptogenic stroke versus known stroke cause (OR=20.74; 95% CI, 4.14-103.90), and cryptogenic stroke versus nonstroke controls (OR=23.9; 95%CI, 3.09-185.42). The association of PFO/ASA abnormalities with stroke was higher in patients who were younger than 55years.26 These studies, however, are largely based on hospitalized patients, possibly reflecting a referral bias. Population based studies do not find such a relationship. For example, PFO was present in 140 of 585 (24.3%) and ASA in 11 (1.9%) randomly sampled subjects older than 45years from Olmstead County, Minnesota.22 The combination of PFO and ASA was present in 6 (4.3%) and was not associated with an increased stroke risk over 5-years.22

Despite this uncertainty, clinical trials have been conducted or are in progress evaluating treatments of patients with stroke in the setting of PFO with or without an ASA. The Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS) was a substudy of the Warfarin-Aspirin Recurrent Stroke Study (WARSS) that randomized patients with otherwise cryptogenic stroke to acetylsalicylic acid as compared to warfarin.30 There was no difference in the rate of stroke or death between those with cryptogenic stroke based on the presence of a PFO and no overall difference in the effect of acetylsalicylic acid versus warfarin on recurrent stroke risk.30 The results of the prospective Spanish multicenter study (CODICIA) were similar.31 In contrast, the Patent Foramen Ovale and Atrial Septal Aneurysm Study found that the combination of PFO and ASA was associated with an increased risk of recurrent strokes (HR 4.17; 95% CI, 1.47-11.84) among patients aged 18 to 55years with cryptogenic stroke who were receiving acetylsalicylic acid.32 The differing results may be due to differences in patient populations (younger cryptogenic stroke patients and only those taking acetylsalicylic acid in the Patent Foramen Ovale and Atrial Septal Aneurysm Study). Currently, there are insufficient data to recommend anticoagulation over acetylsalicylic acid for secondary stroke prevention in patients with PFO or PFO/ASA, and either choice may be reasonable.

The role of endovascular PFO closure for secondary stroke prevention is also uncertain. An open-treatment nonrandomized study comparing percutaneous PFO closure to medical therapy (Vitamin K antagonist or antiplatelet therapy) in patients with cryptogenic stroke did not find an overall benefit of PFO closure after 4years.33 An initial report of the CLOSURE 1 trial, comparing endovascular PFO closure with medical therapy in patients with stroke or TIA, found no benefit from PFO closure, which was associated with several periprocedural complications (presented at AHA Scientific Sessions, November 2010). Other randomized trials of PFO closure for secondary stroke prevention are in progress.

Acute Myocardial Infarction and Left Ventricular Thrombus

There is a short- and long-term increased risk of stroke following MI. Although the exact cause of MI-associated stroke is often unclear, embolization from left ventricular thrombus is a possible mechanism.34 Left ventricular thrombus complicating acute myocardial infarction (AMI) results from turbulent blood flow and stasis related to an akinetic left ventricular wall segment or aneurysm.35 The incidence of left ventricular thrombus was 6.2% in a study of 642 patients with anterior wall AMI followed for 6years, and did not differ between patients treated conservatively, with thrombolysis, or with a primary percutaneous intervention.35 Predictors of left ventricular thrombus were low ejection fraction and severe mitral regurgitation.35

The incidence of stroke in the acute phase following MI is approximately 1%.34 Risk factors include large MI, anterior wall involvement, prior stroke, and increasing age.34 The incidence of stroke was 0.7% at 30days in patients with AMI without persistent ST-segment elevation in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrelin Therapy (PURSUIT) trial that enrolled 10 948 patients; 84% of all strokes were ischemic.36 Strokes occurring after MI resulted in high morbidity and mortality and were predicted by a higher baseline heart rate.36 The long-term risk of stroke following MI is about 6%. Strokes are mainly ischemic. Risk factors include advancing age, diabetes mellitus, previous history of stroke, history of hypertension, and smoking.37

The risk of post-MI stroke may be highest over the first 3 months.38 Some data suggest that treatment with warfarin (target INR, 3.0-4.0) or the combination of acetylsalicylic acid and warfarin (INR, 2.0-2.5) may be more efficacious than acetylsalicylic acid alone in preventing recurrent cardiovascular events after MI, including strokes.39 Warfarin, however, is not generally recommended after MI for stroke prevention unless a stroke or TIA occurs in association with a left ventricular mural thrombus. In this setting, oral anticoagulation with a target INR of 2.5 for at least 3 months is suggested.2 The American College of Chest Physicians guidelines recommend considering moderate intensity oral anticoagulation (INR, 2.0-3.0) in addition to low-dose acetylsalicylic acid (≤100mg/d) for high-risk post-MI patients, including those with a large anterior MI, significant heart failure, intracardiac thrombus, AF, or a history of a thromboembolic event.40

Congestive Heart Failure

Congestive heart failure can lead to cerebral embolism and hypoperfusion-related ischemia, causing both stroke and cognitive impairments.41,42 The risks and mechanisms of cognitive decline with CHF are less well understood than the risk for stroke.43,44,45 Severe CHF can be associated with impaired alertness, behavioral change and cognitive impairment similar to metabolic encephalopathy.43,46 There is not a consistent improvement in neuropsychological functioning in patients with CHF-associated cognitive impairments after cardiac transplantation.47,48,49

Accounting for 9% of strokes, CHF is second after AF as a cause of cardiogenic stroke and CHF and AF coexist in about 2% of stroke patients.42,50 In community studies, CHF is associated with more than a 2-fold increased stroke risk, but much less in clinical trials. Some studies suggest that the risk may increase with decreasing ejection fraction.42,50,51,52,53

The optimal strategy for decreasing stroke risk in the CHF setting is uncertain.2 Two large prospective, randomized, controlled studies assessed whether warfarin is superior to acetylsalicylic acid in patients with a low ejection fraction (ie, ≤35%). The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial compared warfarin to acetylsalicylic acid and clopidogrel to acetylsalicylic acid.54,55 Although stopped early due to poor enrollment, WATCH did not find a difference in the composite endpoint of death, MI or nonfatal stroke, but did find that nonfatal stroke, a secondary outcome, was lower in patients receiving warfarin compared to those receiving acetylsalicylic acid or clopidogrel.56 The Warfarin versus Aspirin in Patients With Reduced Cardiac Ejection Fraction (WARCEF) trial is ongoing and compares warfarin (INR, 2.5-3) versus acetylsalicylic acid (325mg).57 The WATCH and WARCEF investigators have planned a combined analysis. Given the low overall stroke rate in CHF, it may be important to develop a risk stratification scheme similar to the CHADS2 score to identify those at highest stroke risk in order to guide future treatments and enrich clinical trials.50

Native Valvular Heart Disease and Prosthetic Heart Valves

Aortic and mitral valve diseases are associated with an increased stroke risk. A population based study found that patients with mitral stenosis, mitral regurgitation, aortic stenosis, and aortic regurgitation had a higher than expected number of cerebrovascular events. Predictors included advancing age, AF, and severe aortic stenosis.58

Mitral valve prolapse and mitral annular calcification have also been associated with increased stroke risk in some studies.59,60,61 Mitral annular calcification, an uncommon nonrheumatic cause of mitral stenosis predominantly occurring in women, may be associated with stroke because of concomitant aortic atheromas and the risk of embolization of fibrocalcific material. The stroke risk in patients with mitral annular calcification increases with age.2,62

Antithrombotic medications reduce the risk of stroke and systemic embolism in patients with native valvular heart disease, mechanical and bioprosthetic valves, but their use is associated with increased bleeding risk.2 The AHA/American Stroke Association recommends long-term warfarin (INR target, 2.5) in patients with rheumatic mitral valve disease based on the high risk of stroke recurrence, because mitral valvuloplasty does not eliminate embolic risk, and because observational studies indicate that treatment is associated with a lower risk of recurrent embolism.2,63,64,65 In the absence of randomized trials, long-term antiplatelet therapy may be considered in patients with native aortic or nonrheumatic mitral valve disease who have ischemic stroke or TIA.2 For secondary stroke prevention in patients with mechanical prosthetic valves, warfarin (INR target, 3.0; range 2.5-3.5) is recommended over antiplatelet agents.2,66 Acetylsalicylic acid (75 to 100mg/day) may be added to warfarin in patients who have strokes despite adequate anticoagulation and who are not at high risk for bleeding.2,67

Infective Endocarditis

Stroke, mycotic aneurysms, meningitis, and intracerebral abscesses can complicate IE.68 Approximately two-thirds of embolic events in patients with endocarditis involve the central nervous system; 20%-40% of left-sided IE cases are complicated by stroke,most commonly in the middle cerebral artery distribution.16,69,70 Stroke can also be the initial manifestation of IE.15 Intracerebral hemorrhage (ICH) occurs in about 5% of IE due to hemorrhagic infarction or mycotic aneurysmal rupture and is associated with more than 50% mortality.70 Clinically silent cerebral embolism occurs in 30% of patients with mitral or aortic valve endocarditis.71

A multicenter prospective incidence cohort study of 1437 patients with left-sided IE reported a stroke incident rate of 4.82/1000 patient-days over the first week of therapy that fell to 1.71/1000 patient-days in the second week, with a further decline with continued antimicrobial therapy. Stroke risk factors included infection with Staphylococcus aureus, mitral valve vegetations, and myocardial abscess. Other risk factors include mobile vegetations or vegetations >10mm in diameter occurring on the anterior mitral leaflet.70,72,73

Surgery to prevent further embolic complications remains controversial because stroke risk falls dramatically with effective antimicrobial therapy.70 Moreover, the safety of cardiopulmonary bypass following stroke is uncertain due to concerns for intracranial hemorrhage related to anticoagulation during the procedure and potential hemodynamic worsening of the ischemic infarction. Despite these concerns, surgery may still be considered if performed early (ie, within 72h) when embolic rates are highest and when there are other predictors of poor outcome (eg, recurrent embolization, CHF, prosthetic valve IE).74,75 Furthermore, the outcome of stroke patients following cardio-pulmonary bypass may be better than previously thought, with the exception of those with ICH.70,71,76 Large prospective studies quantifying the risk of cardiac surgery after IE-related ICH are lacking, but delaying for 4weeks before cardiac surgery is often recommended.77 The AHA recommends stopping anticoagulation for at least the first 2weeks of antibiotic therapy in the case of recent embolic stroke in the setting of Staphylococcus aureus prosthetic valve IE.74

Neurologic Complications of Cardiac Interventions

Stroke can complicate many cardiac procedures, including percutaneous coronary intervention (PCI), coronary artery bypass operations, valvuloplasty, and catheter ablation for AF. Stroke infrequently complicates PCI (about 0.3%), with the risk increasing with age, advanced renal failure, diabetes mellitus, hypertension, previous stroke, and emergency use of an intra-aortic balloon pump.78,79 Stroke complicating PCI portends high in-hospital and 1-year-mortality.78,79

There are no established guidelines for stroke prevention in the setting of cardiac interventions. Furthermore, the management of stroke in these settings is not straightforward. For example, in the case of stroke complicating cardiac catheterization, intravenous tissue plasminogen activator (IV-tPA) has been contraindicated in patients with MI within the 3 months prior to stroke, previously excluding many of these patients from treatment; recent MI is, however, no longer an absolute contraindication for IV-tPA.80 Other concerns include tPA-related bleeding due to the invasive procedure, concurrent use of antithrombotics, and conjectures about the composition of clots that may be less amenable to lysis.81 There is, however, some evidence that thrombolysis, whether intra-arterial or intravenous, might improve early outcomes after post-catheterization strokes.81

Coronary artery surgery, especially conventional on-pump coronary artery bypass graft, carries a higher rate of stroke and cerebral dysfunction than PCI.6,82 Because of the bleeding risk, IV-tPA is contraindicated for perioperative strokes. Case series suggest reasonable safety and efficacy for intra-arterial thrombolytic therapy; however, adequate controlled studies with appropriate follow-up are lacking.83,84

Although coronary artery bypass graft has been associated with an increased risk of cognitive impairments, studies comparing the cognitive status of patients after coronary artery bypass graft with an appropriate control group of otherwise similar patients with cardiac disease not undergoing coronary artery bypass graft do not find greater decline after the operation.85,86,87 Furthermore, it does not seem to be a sustainable difference in cognitive function in patients who had on-pump versus off-pump coronary artery bypass graft.88

Cardiac complications of neurological disease Cerebrovascular Disease

Just as stroke may complicate a variety of cardiac disorders, cerebrovascular disease can affect the heart. Electrocardiographic (ECG) changes suggesting MI occur in patients with intracerebral hemorrhage, subarachnoid hemorrhage, and 15% to 40% of those with ischemic stroke.89 Stroke can cause large inverted T-waves in anterior ECG leads and a variety of cardiac arrythmias. Severe strokes can cause myocardial cytolysis. Monitoring for cardiac arrythmias and tests for myocardial injury are part of the standard evaluation of stroke patients.83

Neuromuscular Disorders

Cardiac disorders accompany a wide variety of neuromuscular diseases (Table 1).90,91,92 For example, left ventricular hypertrabeculation/noncompaction (LVHT), a cardiac disorder characterized by prominent trabeculations and intertrabecular recesses within the left ventricle, is associated with neuromuscular disorders in up to 80% of cases.93 Cardiac involvement is frequent in mitochondrial disorders and can be the primary determinant of prognosis. Cardiomyopathy may also be the presenting and main feature of Becker muscular dystrophy (BMD) and Emery-Dreifuss muscular dystrophy (EDMD) .94 Depending on the underlying neuromuscular disorder, management of cardiac involvement should be aimed at determining the degree and type of abnormalities, preventing complications and alleviating symptoms.90

Table 1. Neuromuscular Disorders With Cardiac Involvement.

Neuromuscular disorders Mode of inheritance Clinical manifestations Cardiac manifestations
Mitochondrial disorders
Kearns-Sayre Mitochondrial Progressive external ophthalmoplegia, pigmentary degeneration of the retina, short stature, cerebellar ataxia, dementia AV conduction abnormalities AV conduction block
MELAS Mitochondrial Stroke like episodes, lactic acidosis, seizures, dementia LV hypertrophy Dilated cardiomyopathy
MERFF Mitochondrial Myoclonic seizures, cerebellar ataxia, progressive muscular weakness LV hypertrophy Dilated cardiomyopathy
Friedriech's ataxia AR Cerebellar ataxia, dysarthria, loss of proprioception, lower extremities muscle weakness, extensor plantar response, areflexia, diabetes mellitus LV hypertrophy Atrial fibrillation Lateral Q waves on ECG Sudden cardiac death
Muscular dytrophies
Duchenne and Becker muscular dystrophy X-linked Gradually progressive proximal weakness with later involvement of the majority of muscles including respiratory muscles Slower progression in Becker muscular distrophy Subclinical LV dilatation Reduction in LV ejection fraction, severe LV dysfunction, dilated cardiomyopathy and clinical heart failure Conduction blocks, sinus node dysfunction Q waves on ECG mainly in the lateral leads Atrial fibrillation, ventricular tachycardia/fibrillation
Emery Dreifuss muscular dystrophy X-linked, AD, AR Early contractures of the elbows, ankles and cervical spine Slowly progressive weakness that is proximal in the upper limbs and distal in the lower limbs with later involvement of the proximal limb-girdle muscles Severe AV conduction abnormalities including conduction block Bradyarrythmia Atrial fibrillation/flutter Nonsustained ventricular tachycardia LV dilation Dilated cardiomyopathy Sudden cardiac death
Limb girdle muscular dystrophy AD,AR Proximal upper and lower limb-girdle weakness Dilated cardiomyopathy Q waves on ECG mainly in the lateral leads Conduction blocks Atrial fibrillation, ventricular tachycardia Sudden cardiac death
Facioscapulohumeral muscular dystrophy AD Facial, shoulder and upper arm weakness, foot dorsiflexors weakness, hip and pelvis weakness Conduction blocks Possibly stress-induced perfusion abnormalities
Myotonic dystrophy 1 AD Ptosis, weakness of the face, jaw and anterior neck muscles, progressive mucle weakness, myotonia Sinus bradycardia, conduction blocks, atrial fibrillation/flutter LV dysfunction, left atrial dilatation Sudden cardiac death
Diseases of metabolism
Fabry's disease X-linked Multisystemic disease involving the kidneys, nervous system, heart and gastrointestinal system, stroke and neuropathic pain, angiokeratomas, corneal dystrophy LV hypertrophy Heart failure
Pompe disease AR Multisystemic disease, muscle weakness, respiratory failure, macroglossia LV hypertrophy Heart failure

AD, autosomal dominant; AR, autosomal recessive; AV, atrioventricular; ECG, electrocardiogram; LV, left ventricular; MELAS, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes; MERFF, myoclonic epilepsy with ragged red fibers.

Mitochondrial Disorders

Mitochondrial disorders result either from mutations affecting mitochondrial DNA encoding protein subunits of the respiratory chain complexes or from mitochondrial defects originating from nuclear DNA.95,96 Cardiac involvement usually manifests in childhood or early adulthood, can precede the diagnosis of mitochondrial disease, and is associated with increased mortality.95 Cardiac involvement varies between different mitochondrial disorders and can present as hypertrophic myopathy, dilated cardiomyopathy, and conduction abnormalities. Symptoms include CHF, syncope, and sudden death.96

For example, Kearns-Sayre syndrome is characterized by atrioventricular conduction abnormalities that can progress rapidly to complete atrioventricular block, often warranting prophylactic pacemaker implantation.90,97 In contrast, myoclonus epilepsy and ragged red fibers (MERRF) and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are characterized by left ventricular hypertrophy and dilated cardiomyopathy, with asymmetric septal hypertrophy further characterizing MERFF.90 Left ventricular hypertrophy is also the main cardiac manifestation of Friederich ataxia.90

The diagnosis can often be made by mitochondrial enzymatic analysis in skeletal or cardiac muscles biopsies.96 Regardless of cardiac symptoms, cardiac evaluation is recommended for patients with suspected mitochondrial disorders because of the strong association with cardiac disorders and risk for sudden death.

Muscular Dystrophies Duchenne and Becker muscular dystrophies

Duchenne muscular dystrophy (DMD) and BMD result from X-linked mutations in the dystrophin gene on chromosome Xp21. They initially present with proximal weakness that gradually progresses to involve other muscles, including respiratory muscles.94 The dystrophin protein is located on the inner surface of the sarcolemma. It is completely absent or dysfunctional in DMD, but only reduced in BMD.94 Children with DMD typically present with muscle weakness and difficulty reaching motor milestones by the age of 5, whereas patients with BMD may present later and have less muscle weakness. Respiratory and cardiac failures are the leading causes of death in DMD, which usually occurs between the second and third decade.94 In contrast, patients with BMD have a slower progression of weakness and typically survive into adulthood, but heart failure remains an important cause of death and can be the presenting symptom that brings the patient to medical attention.98 Both DMD and BMD female carriers may develop dilated cardiomyopathy without apparent weakness.98 Cardiomyopathy in DMD and BMD is thought to be due to absent or diminished dystrophin in cardiomyocytes.99 Dystrophin deficiency may further increase the susceptibility to myocarditis that may play an additional role in the progression to heart failure.100 In DMD, focal areas of myocardial injury may appear as areas of regional wall abnormalities on cardiac imaging.90 Symptoms of cardiac involvement can be masked by reduced physical activity due to skeletal muscle weakness.99 Left ventricular dysfunction with predilection for wall motion defects in the posterobasal and posterolateral segments can be diagnosed with echocardiography and cardiac magnetic resonance imaging.99,101 Mitral regurgitation can also develop as a result of papillary muscle dysfunction.90 Arrhythmias, including sinus node dysfunction, atrioventricular node dysfunction, AF, and ventricular tachycardia/fibrillation may develop later in the course of the disease.99 Echocardiography and ECG is recommended starting at age 10years in children with DMD.99,102 Treatment of cardiomyopathy includes β blockers, angiotensin-converting enzyme inhibitors, and management of cardiac arrhythmias.99 The angiotensin-converting enzyme inhibitor perindopril preserves systolic function in patients with DMD and decreases mortality.103,104

Emery Dreifuss muscular dystrophy

EDMD can be X-linked or autosomal. The X-linked form is caused by mutations of the STA gene at chromosome Xq28 encoding emerin, a nuclear membrane protein. The autosomal type is caused by a mutation of the LMNA gene at chromosome 1q21 encoding the nuclear lamina proteins, lamins A and C.94 The LMNA mutations cause other pathologies such as dilated cardiomyopathy and conduction system disease, limb-girdle muscular dystrophy with atrioventricular conduction disturbances, an autosomal form of axonal neuropathy, and a rare form of familial partial lipodystrophy.105 Early elbow, ankle and cervical spine contractures characterize EDMD.105 Proximal upper limb and distal lower limb weakness is usually slowly progressive, with later involvement of the proximal limb-girdle muscles.94 Cardiac disease characterized by conduction defects is usually evident by age 30years and may present without muscle weakness.105,106 X-linked EDMD is characterized by AF/flutter, bradyarrhythmia requiring pacemakers, prolongation of PR interval, complete heart block and atrial standstill. Absent P waves due to atrial paralysis is a typical ECG finding.94 Embolic strokes can result from cardiac arrhythmias.105,107 Heart failure occurs mainly in the autosomal forms of EDMD, with symptoms appearing in the third or fourth decades of life.105 Holter monitoring may help early detection of arrhythmias in this population and an ECG should be obtained annually.90 A pacemaker is recommended after sinus node or atrioventricular conduction is apparent.105 Sudden death may still occur after pacemaker placement, possibly due to ventricular tachycardia or fibrillation. An intracardiac defibrillator may be warranted in those with documented symptomatic ventricular arrhythmias.90 Good outcomes following heart transplantation for severe cardiomyopathy in patients with EDMD have been reported.105,107


Cardiac and neurologic diseases frequently overlap. Randomized trials are ongoing to elucidate the best management strategies in many of these disorders, and have been successful in providing certain management guidelines such as for stroke prevention in AF. Similar studies are more difficult for the less common neuromuscular disorders, although not impossible.103,104

Conflicts of interest

None declared.

Received 10 December 2010
Accepted 10 December 2010

Corresponding author: Director, Duke Stroke Center, Box 3651- Duke University Medical Center, Durham, NC 27710, United States.

Cervera A, Amaro S, Obach V, Chamorro A..
Prevention of ischemic stroke: antithrombotic therapy in cardiac embolism..
Curr Drug Targets. , 8 (2007), pp. 824-831
Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al..
American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association..
Stroke. , 42 (2011), pp. 227-276
Hart RG, Pearce LA, Rothbart RM, McAnulty JH, Asinger RW, Halperin JL..
Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators..
J Am Coll Cardiol. , 35 (2000), pp. 183-187
Tayal AH, Tian M, Kelly KM, Jones SC, Wright DG, Singh D, et al..
Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke..
Neurology. , 71 (2008), pp. 1696-1701
Kamel H, Hegde M, Johnson DR, Gage BF, Johnston SC..
Cost-effectiveness of outpatient cardiac monitoring to detect atrial fibrillation after ischemic stroke..
Stroke. , 41 (2010), pp. 1514-1520
Stroke Risk in Atrial Fibrillation Working Group..
Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation..
Stroke. , 39 (2008), pp. 1901-1910
Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ..
Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation..
JAMA. , 285 (2001), pp. 2864-2870
Ezekowitz MD, Bridgers SL, James KE, Carliner NH, Colling CL, Gornick CC, et al..
Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators..
N Engl J Med. , 327 (1992), pp. 1406-1412
Connolly SJ, Laupacis A, Gent M, Roberts RS, Cairns JA, Joyner C..
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study..
J Am Coll Cardiol. , 18 (1991), pp. 349-355
The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med. 1990;323:1505–11..
Stroke Prevention in Atrial Fibrillation Investigators. Stroke Prevention in Atrial Fibrillation Study..
Final results..
Circulation. , 84 (1991), pp. 527-539
Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B..
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study..
Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154:1449–57..
Hylek EM, Skates SJ, Sheehan MA, Singer DE..
An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation..
N Engl J Med. , 335 (1996), pp. 540-546
Heiro M, Nikoskelainen J, Engblom E, Kotilainen E, Marttila R, Kotilainen P..
Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland..
Arch Intern Med. , 160 (2000), pp. 2781-2787
Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet. 1993;342:1255–62..
Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, et al..
Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study BAFTA): a randomised controlled trial..
Lancet. , 370 (2007), pp. 493-503
Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, et al..
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial..
Lancet. , 367 (2006), pp. 1903-1912
Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, et al..
Effect of clopidogrel added to aspirin in patients with atrial fibrillation..
N Engl J Med. , 360 (2009), pp. 2066-2078
ROCKET AF Study Investigators..
Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study..
Am Heart J. , 159 (2010), pp. 340-347e1
Olsson SB..
Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial..
Lancet. , 362 (2003), pp. 1691-1698
Meissner I, Khandheria BK, Heit JA, Petty GW, Sheps SG, Schwartz GL, et al..
Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study..
J Am Coll Cardiol. , 47 (2006), pp. 440-445
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al..
Dabigatran versus warfarin in patients with atrial fibrillation..
N Engl J Med. , 361 (2009), pp. 1139-1151
Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD, et al..
Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale..
Am Heart J. , 159 (2010), pp. 331-339
Hagen PT, Scholz DG, Edwards WD..
Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts..
Mayo Clin Proc. , 59 (1984), pp. 17-20
Overell JR, Bone I, Lees KR..
Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies..
Neurology. , 55 (2000), pp. 1172-1179
O’Gara PT, Messe SR, Tuzcu EM, Catha G, Ring JC..
Percutaneous device closure of patent foramen ovale for secondary stroke prevention: a call for completion of randomized clinical trials. A science advisory from the American Heart Association/American Stroke Association and the American College of Cardiology Foundation..
J Am Coll Cardiol. , 53 (2009), pp. 2014-2018
Halperin JL, Fuster V..
Patent foramen ovale and recurrent stroke: another paradoxical twist..
Circulation. , 105 (2002), pp. 2580-2582
Lethen H, Flachskampf FA, Schneider R, Sliwka U, Kohn G, Noth J, et al..
Frequency of deep vein thrombosis in patients with patent foramen ovale and ischemic stroke or transient ischemic attack..
Am J Cardiol. , 80 (1997), pp. 1066-1069
Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP..
Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study..
Circulation. , 105 (2002), pp. 2625-2631
Serena J, Martí-Fàbregas J, Santamarina E, Rodríguez JJ, Pérez-Ayuso MJ, Masjuan J, et al..
Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study..
Stroke. , 39 (2008), pp. 3131-3136
Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, et al..
Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both..
N Engl J Med. , 345 (2001), pp. 1740-1746
Windecker S, Wahl A, Nedeltchev K, Arnold M, Schwerzmann M, Seiler C, et al..
Comparison of medical treatment with percutaneous closure of patent foramen ovale in patients with cryptogenic stroke..
J Am Coll Cardiol. , 44 (2004), pp. 750-758
Hess DC, D’Cruz IA, Adams RJ, Nichols FT..
Coronary artery disease, myocardial infarction, and brain embolism..
Neurol Clin. , 11 (1993), pp. 399-417
Osherov AB, Borovik-Raz M, Aronson D, Agmon Y, Kapeliovich M, Kerner A, et al..
Incidence of early left ventricular thrombus after acute anterior wall myocardial infarction in the primary coronary intervention era..
Am Heart J. , 157 (2009), pp. 1074-1080
Mahaffey KW, Harrington RA, Simoons ML, Granger CB, Graffagnino C, Alberts MJ, et al..
Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators..
Circulation. , 99 (1999), pp. 2371-2377
Herlitz J, Holm J, Peterson M, Karlson BW, Evander MH, Erhardt L..
Factors associated with development of stroke long-term after myocardial infarction: experiences from the LoWASA trial..
J Intern Med. , 257 (2005), pp. 201-207
Fuster V, Halperin JL..
Left ventricular thrombi and cerebral embolism..
N Engl J Med. , 320 (1989), pp. 392-394
Van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE..
Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial..
Lancet. , 360 (2002), pp. 109-113
Becker RC, Meade TW, Berger PB, Ezekowitz M, O’Connor CM, Vorchheimer DA, et al..
The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)..
Chest. , 133 (2008), pp. S776-S814
Klijn CJ, Kappelle LJ..
Haemodynamic stroke: clinical features, prognosis, and management..
Lancet Neurol. , 9 (2010), pp. 1008-1017
Pullicino PM, McClure LA, Wadley VG, Ahmed A, Howard VJ, Howard G, et al..
Blood pressure and stroke in heart failure in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study..
Stroke. , 40 (2009), pp. 3706-3710
Caplan LR..
Cardiac encephalopathy and congestive heart failure: a hypothesis about the relationship..
Pullicino PM, Hart J..
Cognitive impairment in congestive heart failure?: Embolism vs hypoperfusion..
Neurology. , 57 (2001), pp. 1945-1946
Ackerman RH..
Cerebral blood flow and neurological change in chronic heart failure..
Stroke. , 32 (2001), pp. 2462-2464
Almeida OP, Flicker L..
The mind of a failing heart: a systematic review of the association between congestive heart failure and cognitive functioning..
Intern Med J. , 31 (2001), pp. 290-295
Roman DD, Kubo SH, Ormaza S, Francis GS, Bank AJ, Shumway SJ..
Memory improvement following cardiac transplantation..
J Clin Exp Neuropsychol. , 19 (1997), pp. 692-697
Bornstein RA, Starling RC, Myerowitz PD, Haas GJ..
Neuropsychological function in patients with end-stage heart failure before and after cardiac transplantation..
Acta Neurol Scand. , 91 (1995), pp. 260-265
Schall RR, Petrucci RJ, Brozena SC, Cavarocchi NC, Jessup M..
Cognitive function in patients with symptomatic dilated cardiomyopathy before and after cardiac transplantation..
J Am Coll Cardiol. , 14 (1989), pp. 1666-1672
Pullicino P, Homma S..
Stroke in heart failure: atrial fibrillation revisited?..
J Stroke Cerebrovasc Dis. , 19 (2010), pp. 1-2
Witt BJ, Brown RD, Jacobsen SJ, Weston SA, Ballman KV, Meverden RA, et al..
Ischemic stroke after heart failure: a community-based study..
Am Heart J. , 152 (2006), pp. 102-109
Pullicino PM, Halperin JL, Thompson JL..
Stroke in patients with heart failure and reduced left ventricular ejection fraction..
Neurology. , 54 (2000), pp. 288-294
Katz SD, Marantz PR, Biasucci L, Jondeau G, Lee K, Brennan C, et al..
Low incidence of stroke in ambulatory patients with heart failure: a prospective study..
Am Heart J. , 126 (1993), pp. 141-146
Massie BM..
The year in heart failure: 2004..
J Card Fail. , 11 (2005), pp. 1-6
Massie BM, Krol WF, Ammon SE, Armstrong PW, Cleland JG, Collins JF, et al..
The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics..
J Card Fail. , 10 (2004), pp. 101-112
Massie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, et al..
Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial..
Circulation. , 119 (2009), pp. 1616-1624
Pullicino P, Thompson JL, Barton B, Levin B, Graham S, Freudenberger RS..
Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design..
J Card Fail. , 12 (2006), pp. 39-46
Petty GW, Khandheria BK, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO..
Predictors of cerebrovascular events and death among patients with valvular heart disease: A population-based study..
Stroke. , 31 (2000), pp. 2628-2635
Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL, et al..
Prevalence and clinical outcome of mitral-valve prolapse..
N Engl J Med. , 341 (1999), pp. 1-7
Barnett HJ, Jones MW, Boughner DR, Kostuk WJ..
Cerebral ischemic events associated with prolapsing mitral valve..
Arch Neurol. , 33 (1976), pp. 777-782
Orencia AJ, Petty GW, Khandheria BK, O’Fallon WM, Whisnant JP..
Mitral valve prolapse and the risk of stroke after initial cerebral ischemia..
Neurology. , 45 (1995), pp. 1083-1086
Fulkerson PK, Beaver BM, Auseon JC, Graber HL..
Calcification of the mitral annulus: etiology, clinical associations, complications and therapy..
Am J Med. , 66 (1979), pp. 967-977
Coulshed N, Epstein EJ, McKendrick CS, Galloway RW, Walker E..
Systemic embolism in mitral valve disease..
Br Heart J. , 32 (1970), pp. 26-34
Adams GF, Merrett JD, Hutchinson WM, Pollock AM..
Cerebral embolism and mitral stenosis: survival with and without anticoagulants..
J Neurol Neurosurg Psychiatry. , 37 (1974), pp. 378-383
Szekely P..
Systemic embolism and anticoagulant prophylaxis in rheumatic heart disease..
Br Med J. , 1 (1964), pp. 1209-1212
Mok CK, Boey J, Wang R, Chan TK, Cheung KL, Lee PK, et al..
Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial..
Circulation. , 72 (1985), pp. 1059-1063
Turpie AG, Gent M, Laupacis A, Latour Y, Gunstensen J, Basile F, et al..
A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement..
N Engl J Med. , 329 (1993), pp. 524-529
Ruttmann E, Willeit J, Ulmer H, Chevtchik O, Hofer D, Poewe W, et al..
Neurological outcome of septic cardioembolic stroke after infective endocarditis..
Thomas MP, Wang A..
Clinical problem-solving. Taken out of context..
N Engl J Med. , 359 (2008), pp. 2478-2482
Derex L, Bonnefoy E, Delahaye F..
Impact of stroke on therapeutic decision making in infective endocarditis..
J Neurol. , 257 (2010), pp. 315-321
Snygg-Martin U, Gustafsson L, Rosengren L, Alsio A, Ackerholm P, Andersson R, et al..
Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers..
Clin Infect Dis. , 47 (2008), pp. 23-30
Rohmann S, Erbel R, Gorge G, Makowski T, Mohr-Kahaly S, Nixdorff U, et al..
Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis..
Eur Heart J. , 13 (1992), pp. 446-452
Anderson DJ, Goldstein LB, Wilkinson WE, Corey GR, Cabell CH, Sanders LL, et al..
Stroke location, characterization, severity, and outcome in mitral vs aortic valve endocarditis..
Neurology. , 61 (2003), pp. 1341-1346
Baddour LM, Wilson WR, Bayer AS, Fowler VG, Bolger AF, Levison ME, et al..
Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America..
Circulation. , 111 (2005), pp. e394-434
Horstkotte D, Follath F, Gutschik E, Lengyel M, Oto A, Pavie A, et al..
Task Force Members on Infective Endocarditis of the European Society of Cardiology; ESC Committee for Practice Guidelines (CPG); Document Reviewers. Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary; the task force on infective endocarditis of the European society of cardiology..
Eur Heart J. , 25 (2004), pp. 267-276
Piper C, Wiemer M, Schulte HD, Horstkotte D..
Stroke is not a contraindication for urgent valve replacement in acute infective endocarditis..
J Heart Valve Dis. , 10 (2001), pp. 703-711
Angstwurm K, Borges AC, Halle E, Schielke E, Einhaupl KM, Weber JR..
Timing the valve replacement in infective endocarditis involving the brain..
J Neurol. , 251 (2004), pp. 1220-1226
Dukkipati S, O’Neill WW, Harjai KJ, Sanders WP, Deo D, Boura JA, et al..
Characteristics of cerebrovascular accidents after percutaneous coronary interventions..
J Am Coll Cardiol. , 43 (2004), pp. 1161-1167
Fuchs S, Stabile E, Kinnaird TD, Mintz GS, Gruberg L, Canos DA, et al..
Stroke complicating percutaneous coronary interventions: incidence, predictors, and prognostic implications..
Circulation. , 106 (2002), pp. 86-91
Jauch EC, Cucchiara B, Adeoye O, Meurer W, Brice J, Chan YY, et al..
Part 11: adult stroke: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care..
Circulation. , 122 (2010), pp. S818-S828
Khatri P, Taylor RA, Palumbo V, Rajajee V, Katz JM, Chalela JA, et al..
The safety and efficacy of thrombolysis for strokes after cardiac catheterization..
J Am Coll Cardiol. , 51 (2008), pp. 906-911
Puskas JD, Winston AD, Wright CE, Gott JP, Brown WM, Craver JM, et al..
Stroke after coronary artery operation: incidence, correlates, outcome, and cost..
Ann Thorac Surg. , 69 (2000), pp. 1053-1056
Moazami N, Smedira NG, McCarthy PM, Katzan I, Sila CA, Lytle BW, et al..
Safety and efficacy of intraarterial thrombolysis for perioperative stroke after cardiac operation..
Ann Thorac Surg. , 72 (2001), pp. 1933-1937
Fukuda I, Imazuru T, Osaka M, Watanabe K, Meguro K, Wada M..
Thrombolytic therapy for delayed, in-hospital stroke after cardiac surgery..
Ann Thorac Surg. , 76 (2003), pp. 1293-1295
Selnes OA, Royall RM, Grega MA, Borowicz LM, Quaskey S, McKhann GM..
Cognitive changes 5years after coronary artery bypass grafting: is there evidence of late decline?..
Arch Neurol. , 58 (2001), pp. 598-604
Selnes OA, Grega MA, Borowicz LM, Royall RM, McKhann GM, Baumgartner WA..
Cognitive changes with coronary artery disease: a prospective study of coronary artery bypass graft patients and nonsurgical controls..
Ann Thorac Surg. , 75 (2003), pp. 1377-1384
McKhann GM, Grega MA, Borowicz LM, Bailey MM, Barry SJ, Zeger SL, et al..
Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls..
Van Dijk D, Jansen EW, Hijman R, Nierich AP, Diephuis JC, Moons KG, et al..
Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial..
JAMA. , 287 (2002), pp. 1405-1412
Kopelnik A, Zaroff JG..
Neurocardiogenic injury in neurovascular disorders..
Crit Care Clin. , 22 (2006), pp. 733-752
Bhakta D, Groh WJ..
Cardiac function tests in neuromuscular diseases..
Neurol Clin. , 22 (2004), pp. 591-617
Breton R, Mathieu J..
Usefulness of clinical and electrocardiographic data for predicting adverse cardiac events in patients with myotonic dystrophy..
Can J Cardiol. , 25 (2009), pp. e23-e27
Groh WJ, Groh MR, Saha C, Kincaid JC, Simmons Z, Ciafaloni E, et al..
Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1..
N Engl J Med. , 358 (2008), pp. 2688-2697
Stollberger C, Winkler-Dworak M, Blazek G, Finsterer J..
Association of electrocardiographic abnormalities with cardiac findings and neuromuscular disorders in left ventricular hypertrabeculation/non-compaction..
Cardiology. , 107 (2007), pp. 374-379
Emery AE..
The muscular dystrophies..
Lancet. , 359 (2002), pp. 687-695
Holmgren D, Wahlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M..
Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings..
Eur Heart J. , 24 (2003), pp. 280-288
Marin-Garcia J, Goldenthal MJ, Filiano JJ..
Cardiomyopathy associated with neurologic disorders and mitochondrial phenotype..
J Child Neurol. , 17 (2002), pp. 759-765
Berenberg RA, Pellock JM, DiMauro S, Schotland DL, Bonilla E, Eastwood A, et al..
Lumping or splitting? “Ophthalmoplegia-plus” or Kearns-Sayre syndrome?..
Ann Neurol. , 1 (1977), pp. 37-54
Yokota R, Shirotani M, Kouchi I, Hirai T, Uemori N, Ohta Y, et al..
Subclinical Becker's muscular dystrophy presenting with severe heart failure..
Intern Med. , 43 (2004), pp. 204-208
McNally EM..
Duchenne muscular dystrophy: how bad is the heart?..
Heart. , 94 (2008), pp. 976-977
Mavrogeni S, Papavasiliou A, Spargias K, Constandoulakis P, Papadopoulos G, Karanasios E, et al..
Myocardial inflammation in Duchenne Muscular Dystrophy as a precipitating factor for heart failure: a prospective study..
BMC Neurol. , 10 (2010), pp. 33
Yilmaz A, Gdynia HJ, Baccouche H, Mahrholdt H, Meinhardt G, Basso C, et al..
Cardiac involvement in patients with Becker muscular dystrophy: new diagnostic and pathophysiological insights by a CMR approach..
J Cardiovasc Magn Reson. , 10 (2008), pp. 50
Bushby K, Muntoni F, Bourke JP..
107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands..
Neuromuscul Disord. , 13 (2003), pp. 166-172
Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Becane HM..
Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy..
J Am Coll Cardiol. , 45 (2005), pp. 855-857
Duboc D, Meune C, Pierre B, Wahbi K, Eymard B, Toutain A, et al..
Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow-up..
Am Heart J. , 154 (2007), pp. 596-602
Boriani G, Gallina M, Merlini L, Bonne G, Toniolo D, Amati S, et al..
Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study..
Vohanka S, Vytopil M, Bednarik J, Lukas Z, Kadanka Z, Schildberger J, et al..
A mutation in the X-linked Emery-Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy..
Neuromuscul Disord. , 11 (2001), pp. 411-413
Kichuk Chrisant MR, Drummond-Webb J, Hallowell S, Friedman NR..
Cardiac transplantation in twins with autosomal dominant Emery-Dreifuss muscular dystrophy..
J Heart Lung Transplant. , 23 (2004), pp. 496-498
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