TOYAMA, JAPAN. Extensive research has shown that the main factor determining left atrium clot formation and associated stroke risk is the rate at which blood flows in and out of the left atrial appendage (LAA). If this rate is high then the formation of a clot or the precursors of a clot (smoke-like echoes [spontaneous echo contrast or SEC] on a transesophageal echocardiogram) is very unlikely.

Factors that can reduce the flow rate through the LAA include aging, congestive heart failure, poor left ventricular ejection fraction, elevated levels of hematocrit or von Willebrand factor, and a prior ischemic stroke or transient ischemic attack (TIA). Fortunately, a recent Japanese study concluded that lone afibbers and patients with atrial flutter are at very low risk for thrombus formation in the LAA. Now a group of researchers from Toyama University report that the presence of severe mitral regurgitation (MR), including mitral valve prolapse, increases the flow of blood in and out of the LAA and thus is associated with a substantially lower risk of clot formation.

Their study included 271 patients (average age of 67 years) with permanent atrial fibrillation who underwent both transthoracic and transesophageal echocardiography (TEE) and also had blood samples taken to measure markers of blood clotting, notably D-dimer. NOTE: Fibrin monomers and dimers polymerize into blood cots through the action of activated coagulation factor XIII. The patients investigated were by no means lone afibbers – about 40% had hypertension, 25% had heart failure, 25% had a history of stroke or TIA, and 56% were on warfarin. Of the 271 patients, 20 (7%) had severe MR including 9 patients with mitral valve prolapse, 45 (17%) had moderate MR, and 92 (34%) had mild MR as determined with TEE. The TEE study found that patients with severe MR had a higher average LAA peak flow velocity (35.2 cm/s) than did those with no or only mild MR (25.5 cm/s). In addition, the severity of SEC was significantly lower in patients with severe MR (0.7) than in those with moderate (1.7), mild (2.2) or no MR (1.9). The level of D-dimer was surprisingly low (0.76 mcg/mL) in patients with severe MR and highest (1.72) in those with moderate MR. Patients with no MR had an average D-dimer level of 0.82. Warfarin therapy had no effect on d-dimer levels or presence of SEC.

The Japanese researchers conclude that patients with severe MR, including mitral valve prolapse, have a lower thromboembolic risk than do those with mild or moderate MR. They speculate that the more "chaotic" blood flow resulting from severe MR helps prevent blood stasis in the LAA. They suggest that the increased D-dimer levels found among patients with moderate MR may be associated with their heart failure, but caution that the higher D-dimer levels and SEC values found among these patients could increase their risk of thromboembolism.

Fukuda, N, et al. Relation of the severity of mitral regurgitation to thromboembolic risk in patients with atrial fibrillation. International Journal of Cardiology, August 5, 2009 [Epub ahead of print]

Editor's comment: In an earlier LAF survey 7% of respondents reported that they had been diagnosed with mitral valve prolapse, while 14% had mild regurgitation. Although there is no evidence that lone afibbers with intact left ventricular ejection fraction are at increased risk for LAA blood stasis, SEC or thrombus formation, it is comforting to learn that the presence of severe mitral valve regurgitation, including mitral valve prolapse, does not increase stroke risk, but is actually protective against thromboembolism.