How can Shone syndrome increase the risk of embolic stroke in patients with this congenital heart defect?

How Shone Syndrome Causes Embolic Stroke

Shone syndrome increases embolic stroke risk primarily through paradoxical embolization across intracardiac shunts (particularly atrial-level communications), cardiac dysfunction with atrial arrhythmias leading to thrombus formation, and the presence of multiple obstructive left-sided lesions that promote blood stasis and endothelial dysfunction. 1

Primary Mechanisms of Stroke in Shone Syndrome

Paradoxical Embolization Through Intracardiac Shunts

• Complex congenital heart lesions with right-to-left shunting are particularly prone to cause stroke, allowing venous thrombi to bypass the pulmonary circulation and directly enter the systemic arterial circulation 1
• Emboli can arise at the atrial level (such as atrial septal defects with pulmonary hypertension), at the ventricular level (ventricular septal defects with pulmonary hypertension), or at the arterial level 1
• Patients with atrial-level shunts and mitral obstruction (a key feature of Shone syndrome with supravalvular mitral ring and parachute mitral valve) are specifically identified as at-risk for stroke 1

Cardiac Dysfunction and Atrial Arrhythmias

• Elevated left atrial pressure from mitral inflow obstruction leads to pulmonary venous hypertension and atrial enlargement, creating conditions favorable for thrombus formation 2
• Left ventricular pressure overload from outflow obstruction (subaortic stenosis and coarctation) causes hypertrophy and eventual diastolic dysfunction, further compromising cardiac hemodynamics 2
• Atrial arrhythmias, particularly atrial fibrillation, place patients with structural heart disease at additional stroke risk through stasis and thrombus formation in the left atrium 1
• Congestive heart failure with reduced ejection fraction increases the risk of embolism regardless of the underlying cause 1

Prothrombotic State in Complex Congenital Heart Disease

• Patients with cyanotic congenital heart disease demonstrate evidence of increased platelet aggregation with higher levels of platelet P-selectin and thrombin-antithrombin complex, and lower levels of protein C activity 1
• Endothelial dysfunction is known to be present in cyanotic patients, contributing to a prothrombotic milieu 1
• Children with stroke and heart disease have an increased prevalence of ≥1 prothrombotic abnormalities, including lipoprotein(a), anticardiolipin antibodies, and protein C deficiency 1

Additional Compounding Risk Factors

Surgical and Procedural Risks

• Risk factors are compounded by the added risk of surgery and endovascular procedures, which are frequently required in Shone syndrome management 1
• Over 70% of patients with Shone syndrome require reoperation during follow-up, creating multiple opportunities for perioperative thromboembolic events 2
• Cardiac catheterizations necessary for diagnosis or therapy may be complicated by thrombosis 1

Iron Deficiency in Cyanotic Patients

• Iron deficiency in cyanotic patients, often caused by repeat phlebotomy, can lead to stroke, possibly as a result of reduced oxygen-carrying capacity of red blood cells 1
• This mechanism is particularly relevant if Shone syndrome is associated with cyanosis from incomplete repair or residual shunting 1

Clinical Implications for Stroke Prevention

Anticoagulation Considerations

• It is reasonable to initiate systemic anticoagulation in children with stroke from confirmed or suspected cardiac embolism (not related to patent foramen ovale) 1
• For subsequent decisions on anticoagulation duration, consider the nature and expected management of the heart defect, presence of additional stroke risk factors such as thrombophilia, and presence of cervical or cerebral vascular disease 1
• In patients with atrial-level shunts and mitral obstruction (characteristic of Shone syndrome), anticoagulation should be strongly considered, particularly if atrial arrhythmias are present 1

Surveillance Requirements

• All patients with Shone syndrome require lifelong cardiology follow-up by adult congenital heart disease specialists, with key surveillance including annual echocardiography and assessment for arrhythmias 2
• Expanded evaluation for inherited or acquired prothrombotic risk factors is reasonable in patients who have experienced a first stroke, including protein C, protein S, antithrombin III, lipoprotein(a), homocysteine, anticardiolipin antibodies, lupus anticoagulant, factor V Leiden, and prothrombin gene mutations 1

Common Pitfalls to Avoid

• Do not assume that antiplatelet therapy alone is sufficient in patients with significant structural heart disease and intracardiac shunts—these patients typically require anticoagulation 1
• Recognize that stroke risk persists even after surgical repair if residual shunts, atrial arrhythmias, or ventricular dysfunction remain 1
• Iron deficiency should be avoided in cyanotic patients through judicious use of phlebotomy 1