Left Atrial Appendage Thrombus

Left atrial appendage (LAA) thrombus is thrombus in the trabeculated, blind ended appendage of the left atrium. It is the source of most cardioembolic strokes in atrial fibrillation.

Transoesophageal echocardiography finds it in about 1 to 3% of patients with atrial fibrillation before cardioversion or ablation, and in more patients with a high stroke score, persistent atrial fibrillation or rheumatic mitral stenosis. Even patients on anticoagulation carry a small prevalence.

Risk factors are a high CHA2DS2-VASc score, non-paroxysmal atrial fibrillation, low appendage emptying velocity (under 20 cm/s), dense spontaneous echo contrast, enlarged left atrium, reduced ejection fraction, heart failure, previous stroke, non-chicken-wing appendage shape, cardiac amyloidosis, hypertrophic cardiomyopathy, and subtherapeutic or interrupted anticoagulation.

In sub-Saharan Africa, rheumatic mitral stenosis with atrial fibrillation is common, and poor INR control raises the prevalence.

Pathophysiology. Atrial remodelling and loss of contraction cause stasis in the appendage. Endothelial dysfunction and a prothrombotic state complete the triad. Cardioversion, pharmacological or electrical, can dislodge the thrombus.

• Usually asymptomatic. Found during pre-cardioversion or pre-ablation imaging, or after an embolic event.
• Atrial fibrillation symptoms: palpitations, dyspnoea, fatigue.
• Embolism: stroke, transient ischaemic attack, limb, renal, splenic or mesenteric ischaemia.

Red flags.

• Stroke, transient ischaemic attack or other systemic embolism
• Mobile or protruding thrombus
• Thrombus despite 3 weeks or more of therapeutic anticoagulation
• Rheumatic mitral stenosis or a mechanical valve
• Haemodynamic instability needing urgent cardioversion

• CHA2DS2-VASc score. Heart failure 1, hypertension 1, age 75 years or over 2, diabetes 1, stroke, transient ischaemic attack or thromboembolism 2, vascular disease 1, age 65 to 74 years 1, female sex 1.
• Transoesophageal echocardiography. The reference test. Multiplanar views (0 to 135 degrees) show an echo dense mass distinct from the pectinate muscles, seen in more than one plane. Also appendage emptying velocity and spontaneous echo contrast.
• Cardiac CT with delayed phase imaging at 30 to 90 seconds: a persistent filling defect indicates thrombus, while an early filling defect that fills later is slow flow. Intracardiac echocardiography and cardiac MRI are alternatives.
• Anticoagulation review. Adherence, dosing against renal function, interacting drugs, and INR history.
• Laboratory. Creatinine, haemoglobin, liver function, INR, thyroid function.

Differential diagnosis.

• Pectinate muscles and trabeculations
• The left atrial ridge between the appendage and left upper pulmonary vein
• Dense spontaneous echo contrast (sludge), which carries high risk without being thrombus
• Left atrial myxoma or other tumour
• Appendage aneurysm
• Air or artefact after instrumentation
• Appendage occlusion device thrombus

Defer cardioversion and ablation. Anticoagulate and re-image.

• Therapeutic anticoagulation for at least 3 weeks (up to 6 weeks), then repeat transoesophageal echocardiography or CT. Thrombus resolves in about 60 to 80%. If it has resolved, proceed to cardioversion or ablation, with uninterrupted anticoagulation for at least 4 weeks afterwards and long term by risk.
• Apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Reduce or avoid with strong dual CYP3A4 and P-glycoprotein inhibitors (ketoconazole, ritonavir).
• Rivaroxaban 20 mg orally once daily with the main meal (15 mg at creatinine clearance 15 to 49 mL/min, avoided under 15 mL/min, contraindicated in moderate or severe liver disease with coagulopathy). Avoid with strong dual CYP3A4 and P-glycoprotein inhibitors.
• Warfarin 5 mg orally once daily at the start (2 to 3 mg in older adults, liver impairment or interacting drugs), adjusted to an INR of 2.0 to 3.0, no fixed maximum, with INR every 2 to 3 days at the start, weekly until stable, then every 4 to 12 weeks. Use warfarin, with direct oral anticoagulants avoided, in moderate or severe rheumatic mitral stenosis and with mechanical valves.
• Rate control, not rhythm control, until resolution. Bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to 10 mg once daily, maximum 10 mg daily in heart failure (otherwise 2.5 to 10 mg, maximum 20 mg daily, and not over 10 mg daily at creatinine clearance under 20 mL/min or in severe liver impairment). Contraindicated in cardiogenic shock, high grade atrioventricular block without a pacemaker, sick sinus syndrome and severe asthma. Digoxin 62.5 to 125 microgram orally once daily, maximum 250 microgram daily, with a level of 0.5 to 0.9 ng/mL taken at least 6 hours after the dose (62.5 microgram at eGFR under 30 mL/min/1.73 m2, in older adults and at low body weight).
• Avoid drugs that can restore sinus rhythm (amiodarone, flecainide, propafenone, ibutilide, vernakalant) until the thrombus has gone, because conversion can dislodge it.
• Persistent thrombus after 6 weeks of therapeutic anticoagulation. Confirm adherence and levels. Options with limited data are switching the anticoagulant (direct oral anticoagulant to warfarin, or to another agent), aiming for the upper half of the INR range (2.5 to 3.0), or adding aspirin 75 to 100 mg once daily when bleeding risk is low. Continue anticoagulation long term. Appendage occlusion devices are contraindicated while thrombus is present. Surgical excision or exclusion of the appendage is an option at cardiac surgery.
• Unstable arrhythmia needing urgent cardioversion. Proceed with synchronised cardioversion at 120 to 200 J biphasic under sedation despite thrombus when life is threatened, start anticoagulation, and accept the embolic risk.
• Embolic event. Treat the event in the usual way, with the timing of anticoagulation after stroke set by imaging (about 1 day after a transient ischaemic attack, 3 days after a minor stroke, 6 days after a moderate stroke and 12 to 14 days after a major stroke; timing is contested).
• Prevention. Maintain a time in therapeutic INR range over 70%, support adherence, and avoid interrupting anticoagulation. Use of a direct oral anticoagulant is preferred over warfarin when poor INR control occurs, except in rheumatic mitral stenosis and mechanical valves.

Special groups.

• Rheumatic mitral stenosis: warfarin only, with a target INR of 2.0 to 3.0, and early referral for valve intervention.
• Kidney impairment: reduce apixaban to 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min and avoid it under 15 mL/min, give rivaroxaban 15 mg at creatinine clearance 15 to 49 mL/min and avoid it under 15 mL/min, with creatinine every 6 months at age 75 years or over or creatinine clearance 30 to 60 mL/min.
• Pregnancy: warfarin is teratogenic in weeks 6 to 12, and direct oral anticoagulants are avoided in pregnancy and breastfeeding. Use enoxaparin 1 mg/kg subcutaneously every 12 hours with a peak anti-Xa of 0.8 to 1.2 IU/mL 4 to 6 hours after the dose (1 mg/kg once daily at creatinine clearance under 30 mL/min).

Monitoring. Transoesophageal echocardiography or CT at 3 to 6 weeks. INR every 4 to 12 weeks once stable. Creatinine, haemoglobin and bleeding review at each visit. Ambulatory ECG for rhythm. Neurological review after any embolic event.

Referral and escalation. Refer to cardiology or electrophysiology. Urgent for embolism, mobile thrombus, thrombus persisting on anticoagulation, or an unstable patient who needs cardioversion.