Cardioembolic stroke: everything has changed

Abstract

Historically, because of the difficulty of using warfarin safely and effectively, many patients with cardioembolic stroke who should have been anticoagulated were instead given ineffective antiplatelet therapy (or no antithrombotic therapy). With the arrival of new oral anticoagulants that are not significantly more likely than aspirin to cause severe haemorrhage, everything has changed. Because antiplatelet agents are much less effective in preventing cardioembolic stroke, it is now more prudent to anticoagulate patients in whom cardioembolic stroke is strongly suspected. Recent advances include the recognition that intermittent atrial fibrillation is better detected with more prolonged monitoring of the cardiac rhythm, and that percutaneous closure of patent foramen ovale (PFO) may reduce the risk of stroke. However, because in most patients with stroke and PFO the PFO is incidental, this should be reserved for patients in whom paradoxical embolism is likely. A high shunt grade on transcranial Doppler saline studies, and clinical clues to paradoxical embolism, can help in appropriate selection of patients for percutaneous closure. For patients with atrial fibrillation who cannot be anticoagulated, ablation of the left atrial appendage is an emerging option. It is also increasingly recognised that high levels of homocysteine, often due to undiagnosed metabolic deficiency of vitamin B₁₂, markedly increase the risk of stroke in atrial fibrillation, and that B vitamins (folic acid and B₁₂) do prevent stroke by lowering homocysteine. However, with regard to B₁₂, methylcobalamin should probably be used instead of cyanocobalamin. Many important considerations for judicious application of therapies to prevent cardioembolic stroke are discussed.

Figure 1

Measurement of plaque burden adds to the diagnosis of stroke subtype. (A) Although it may be intuitive that patients without stenosis do not have much plaque, in fact many patients without carotid stenosis of 50% or more have large artery disease, with a high total plaque area (TPA). This is thought to be due to compensatory enlargement of the artery, as described by Glagov et al. This composite drawing of carotid plaques from the ultrasound report of a normotensive 79-year-old woman with atherosclerotic stroke shows a very high plaque burden (TPA=4.71 cm², approximately nine times normal for age and sex); the peak velocities (numbers written into the lumen) show that there was no internal carotid stenosis. (B) In contrast, this composite drawing shows almost no plaque (TPA=0.06 cm²) in a normotensive 72-year-old man with no carotid stenosis and cryptogenic stroke (normal TPA for age and sex would be more than 10 times higher—0.8 cm²). The absence or near absence of plaque in a normotensive patient without diabetes raises the suspicion of a cardioembolic source, dissection or other unusual cause of stroke. L, left; R, right. (Reproduced with permission of Karger from Bogiatzi et al 14).

Figure 2

Transcranial Doppler screenshots of Spencer shunt grades are shown for examples of cases missed by transoesophageal echocardiography with sedation. It can be seen that the presence of bubbles in the cerebral arteries is obvious; besides the visual output on the screen, a loud signal is heard from the audio output with each bubble crossing the patent foramen ovale. Grade 0, no microemboli detected; grade 1, 1–10 microemboli; grade 2, 11–30 microemboli; grade 3, 31–100 microemboli; grade 4, 101–300 microemboli; grade 5, >300 microemboli. (Reproduced with permission of Elsevier from Tobe et al 7)

Figure 3

Age distribution of increased plasma total homocysteine (≥14 μmol/L) among patients referred to vascular prevention clinics. Among patients attending secondary stroke prevention clinic of JDS at University Hospital in London, Canada, the prevalence of a plasma total homocysteine >14 µmol/L is more than 40% at age 80 and higher: precisely the age group in which atrial fibrillation is the most common cause of stroke. (Reproduced with permission of Elsevier from Spence D. Mechanisms of thrombogenesis in atrial fibrillation. Lancet 2009 Mar 21;373 (9668):1006).

Figure 4

Probability of major bleeding event and ischaemic stroke/SEE versus trough plasma concentration of dabigatran. Calculated for a 72-year-old male patient with atrial fibrillation with prior stroke and diabetes. Lines and boxes at the top of the panel indicate median dabigatran concentrations in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial with 10th and 90th percentiles. Conc, one-fourth concentration; DE, one-fourth dabigatran etexilate; SEE, one-fourth systemic embolic event(s). (Reproduced with permission of Elsevier from Reilly et al 39).