Cardioembolic Stroke

Cardioembolic stroke is ischaemic stroke caused by a thrombus or other embolic material from the heart or aortic arch. It accounts for about 20 to 30% of ischaemic strokes and tends to be larger and more disabling than other subtypes.

Atrial fibrillation causes about half of cardioembolic strokes and raises stroke risk about fivefold. Prevalence of atrial fibrillation rises from under 1% under age 60 to over 10% over age 80.

Sources. Atrial fibrillation or flutter, recent myocardial infarction with left ventricular thrombus, dilated cardiomyopathy, rheumatic mitral stenosis, mechanical valves, infective and non-bacterial endocarditis, atrial myxoma and paradoxical embolism through a patent foramen ovale.

Features that suggest it. Sudden maximal onset, cortical signs, multiple territories, haemorrhagic transformation, and a previous embolus to another organ.

Risk scoring in atrial fibrillation. The CHA2DS2-VASc score assigns 1 point each for heart failure, hypertension, age 65 to 74, diabetes, vascular disease and female sex, and 2 points each for age 75 or over and previous stroke or TIA.

Pathophysiology.

Stasis in a fibrillating atrium or hypokinetic ventricle, endothelial injury and a hypercoagulable state (Virchow triad) lead to thrombus formation, commonly in the left atrial appendage.

Embolisation abruptly occludes a large intracranial vessel, with limited collateral supply, and reperfusion may cause haemorrhagic transformation.

• Sudden onset of focal deficit, often maximal at onset, with aphasia, neglect, hemianopia or gaze deviation.
• Reduced consciousness in large hemispheric infarcts.
• Irregularly irregular pulse, murmurs, signs of heart failure or embolic phenomena in other organs.
• Fever, new murmur or embolic skin signs suggest endocarditis.

Red flags.

• Fever with a new murmur or a history of intravenous drug use (endocarditis).
• Large infarct with early swelling or reduced consciousness.
• Headache, vomiting or deterioration after thrombolysis or after anticoagulation (haemorrhagic transformation).

• Urgent non-contrast CT, with CT angiography and perfusion imaging when thrombectomy or late window treatment is considered; MRI with diffusion weighted sequences otherwise.
• 12 lead ECG, then ambulatory monitoring for at least 24 hours, extended to 14 to 30 days or implantable loop recorder in cryptogenic stroke.
• Transthoracic echocardiography, with transoesophageal echocardiography for suspected endocarditis, left atrial appendage thrombus or aortic arch atheroma.
• Blood tests: full blood count, coagulation screen, glucose, creatinine, troponin; blood cultures when endocarditis is suspected.

Differential diagnosis. Large artery atherothrombosis, small vessel disease, arterial dissection, vasculitis, hypercoagulable states, intracranial haemorrhage, seizure with postictal paresis, hypoglycaemia and migraine aura.

• Intravenous thrombolysis within 4.5 hours of onset when criteria are met, then thrombectomy for large vessel occlusion.
• Alteplase 0.9 mg/kg intravenously (maximum 90 mg), 10% as a bolus over 1 minute and the rest as an infusion over 60 minutes, within 4.5 hours of onset or last known well. Monitor neurological observations and blood pressure every 15 minutes for 2 hours, every 30 minutes for the next 6 hours, then hourly to 24 hours; keep blood pressure under 185/110 mmHg before and under 180/105 mmHg after treatment; repeat imaging at 24 hours or with deterioration. Contraindicated with previous intracranial haemorrhage, INR over 1.7, platelets under 100 x 10^9/L, glucose under 2.7 mmol/L, anticoagulant use within 48 hours, major surgery within 14 days, or endocarditis; no renal adjustment.
• Tenecteplase 0.25 mg/kg intravenously as a single bolus over 5 to 10 seconds (maximum 25 mg), within 4.5 hours, with the same monitoring and contraindications as alteplase; no renal adjustment.
• Mechanical thrombectomy for occlusion of the internal carotid or proximal middle cerebral artery within 6 hours, and in selected patients to 24 hours on perfusion imaging.
• Anticoagulation: start early after repeat imaging excludes major haemorrhagic transformation, from 48 hours for minor or moderate stroke and about day 6 or 7 for major stroke.
• Apixaban 5 mg orally twice daily, long term. Maximum 10 mg daily. Monitor renal function and full blood count at least yearly, and every 6 months when eGFR is under 60 or age is over 75. Reduce to 2.5 mg twice daily when two of the following apply: age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over; also 2.5 mg twice daily when creatinine clearance is 15 to 29 mL/min; avoid when under 15 mL/min, with strong CYP3A4 and P-glycoprotein interacting drugs, in severe hepatic impairment and in pregnancy.
• Rivaroxaban 20 mg orally once daily with the evening meal, long term. Maximum 20 mg daily. Monitor renal function, liver enzymes and full blood count at least yearly. Use 15 mg daily when creatinine clearance is 15 to 49 mL/min; avoid when under 15 mL/min, in moderate or severe hepatic impairment, with strong CYP3A4 and P-glycoprotein interacting drugs, and in pregnancy.
• Dabigatran 150 mg orally twice daily, long term. Maximum 300 mg daily. Monitor renal function at least yearly, and every 6 months when over age 75 or creatinine clearance is under 50 mL/min. Use 110 mg twice daily at age 80 or over, with verapamil, or with high bleeding risk; contraindicated when creatinine clearance is under 30 mL/min, with strong P-glycoprotein inhibitors and in pregnancy; idarucizumab reverses it.
• Edoxaban 60 mg orally once daily, long term. Maximum 60 mg daily. Monitor renal function and full blood count at least yearly. Use 30 mg daily when creatinine clearance is 15 to 50 mL/min, weight is 60 kg or under, or with ciclosporin, dronedarone, erythromycin or ketoconazole; avoid when under 15 mL/min and in pregnancy; efficacy is reduced when creatinine clearance is over 95 mL/min.
• Mechanical heart valves and moderate to severe rheumatic mitral stenosis: warfarin, not a direct oral anticoagulant. Warfarin initial dose 5 mg orally once daily in the evening for 2 days (2 to 3 mg in older adults, hepatic impairment and heart failure), then adjusted to INR; no fixed maximum. Target INR 2.0 to 3.0 (2.5 to 3.5 for mechanical mitral valves). Monitor INR daily at first, then every 3 to 5 days, and every 4 to 12 weeks when stable. Reduce dose in hepatic impairment; avoid in the first trimester of pregnancy and use low molecular weight heparin under specialist care.
• Left ventricular thrombus: anticoagulation for at least 3 months. Left atrial appendage closure for patients who cannot take long term anticoagulants.
• Endocarditis: avoid thrombolysis and start antibiotics; delay anticoagulation and decide with cardiology and neurosurgery.
• Blood pressure under 130/80 mmHg, LDL cholesterol under 1.8 mmol/L and good diabetes control.

Monitoring. Review at 1 week, 3 months and yearly; check renal function, adherence and bleeding.

Referral and escalation. Stroke unit admission; cardiology for rhythm control, valve disease and left atrial appendage closure; neurosurgery for malignant oedema.

Special groups. Pregnancy: warfarin is teratogenic and direct oral anticoagulants are avoided; use low molecular weight heparin. Older adults: dose by renal function and weight.