Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores

Shadi Yaghi, MD; Hooman Kamel, MD


Stroke. 2017;48(10):2665-2670. 

In This Article

Prediction of Stroke Risk Based on Structural and Functional Markers

Markers Related to the Left Atrium

Left atrial (LA) enlargement can potentiate stasis and endothelial injury, thereby potentially leading to thrombus formation. In the general population of patients regardless of AF status, LA enlargement is associated with ischemic stroke risk,[50] particularly of embolic subtypes.[51] In patients with AF, studies showed an association between LA enlargement and stroke and systemic embolism.[52,53] In another study of 2713 patients, LA diameter >45 mm was associated with the risk of ischemic stroke even after adjustment for the CHA2DS2-VASc score (HR, 1.74; 95% CI, 1.25–1.83). Furthermore, in a study of patients with AF being treated with either a vitamin-K antagonist (warfarin) or a non–vitamin-K antagonist oral anticoagulation drug, 2.7% had a LAA thrombus seen on transesophageal echocardiogram (TEE), despite compliance with anticoagulation.[54] Those with thrombus had a mean LA diameter of 47 mm compared with 41 mm in those without thrombus (P=0.003).[54]

Markers Related to the LAA

The LAA is the main origin of thrombi in patients with AF.[55] Reduced LAA flow velocity on echocardiography is a marker of LAA stasis. A cross-sectional study of patients with AF showed that those with prior stroke had a lower LAA flow velocity (36 cm/s) than those without stroke (55 cm/s; P<0.001).[56] Furthermore, in a post hoc analysis of 721 patients from the SPAF-III trial who underwent TEE, peak anterograde (emptying) LAA flow velocity <20 cm/s was independently associated with LAA thrombus (RR, 2.6; P=0.02).[57]

Spontaneous echocardiographic contrast is a dynamic smoke-like appearance pattern not uncommonly seen on TEE and considered to be a marker of hypercoagulability, stasis, and aggregation of red blood cells.[58] In an analysis of 382 patients undergoing TEE in the SPAF trials, spontaneous echocardiographic contrast was detected in ≍63% of patients and was independently associated with LAA thrombus and future thromboembolic events.[59]

In addition to biomarkers of LAA dysfunction, the morphology and structure of the LAA are other determinants of stroke risk. In a cross-sectional study of 932 patients with AF who underwent TEE, ≍8% had a history of ischemic stroke or TIA. The morphological appearance of the LAA was classified as chicken wing in 48% of patients, windsock in 19%, cactus in 30%, and cauliflower in 3%. After adjusting for known stroke risk factors, morphologies other than chicken wing were associated with higher odds of stroke: cauliflower (odds ratio, 8.0; P=0.056), windsock (odds ratio, 4.5; P=0.038), and cactus (odds ratio, 4.08; P=0.046).[60] Other studies in AF also found an inverse association between chicken-wing morphology and stroke risk and covert brain infarcts.[61] The mechanistic basis of these associations may be related to a higher LAA flow velocity in patients with chicken-wing morphology as compared with non–chicken-wing morphology.[61] On the contrary, the association between a cauliflower morphology and stroke was confirmed by another study showing that extensive trabeculations, which are often seen with the cauliflower morphology, were independently associated with stroke.[62]

Besides the morphological shape of the LAA, a larger orifice size[56] and higher number of lobes[63] have also been associated with thromboembolic risk.

In addition to visualizing the LAA, cardiac magnetic resonance imaging can characterize tissue changes, such as fibrosis and scarring,[64] and more recently, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging has been used to evaluate the degree of fibrosis in patients with AF.[65] In a study comparing cardiac magnetic resonance imaging and TEE, there was an association between the degree of atrial fibrosis on cardiac magnetic resonance imaging and the detection of thrombus or spontaneous echo contrast on echocardiography (odds ratio, 3.6; P<0.01).[66]

Clinical trials showed that in patients with AF, LAA closure was noninferior to warfarin in reducing stroke risk, suggesting a structural and functional role of the LAA in determining stroke risk in patients with AF.[67] Much of this benefit, however, was driven by a reduction in hemorrhagic stroke, so it remains unclear whether closure is as protective against ischemic stroke as anticoagulation, particularly if compared with direct oral anticoagulants, which have a significantly lower risk of intracranial hemorrhage than warfarin.