In the past a lot of interest has been taken in identifying patients with AF who are at an increased risk of thromboembolism. Clinical risk factor have been well established. In addition, to assess the individual risk of thromboembolism clinically, TOE enables collection of further evidence of an increased thromboembolic risk. Previous studies showed that the presence of SEC—a phenomenon of slow flow in the atria—and depressed mechanical function of the LAA predispose to atrial thrombosis and are associated with an increased risk of thromboembolism.12 Leung and colleagues13 observed an annual thromboembolic event rate of 12% in patients with SEC compared with only 3% in patients without SEC. The SPAF III investigators found a relative risk of 2.7 for thromboembolism in patients with dense SEC.14 Moreover, they observed that SEC was more frequent in the high risk patient group. However, it is not clear whether TOE risk assessment of thromboembolism adds to the clinical assessment of embolic risk in patients with AF. Furthermore, the incidence of a thrombogenic milieu in patients without clinical risk factors is unknown.
Relation between clinical and TOE risk factors for thromboembolism
Our data show that a history of hypertension, a history of diabetes mellitus, and age > 65 years were all significantly related to the TOE finding of a thrombogenic milieu. In addition, LVEF < 45% was strongly associated with a thrombogenic milieu. The last finding is consistent with the results of previous TOE studies, which found that chronic heart failure and structural heart disease are predisposing factors for thromboembolism.
21,22 Therefore, our data support the current guidelines for anticoagulation stating that older patients and patients with other clinical risk factors have an increased risk of thromboembolism.
23 Interestingly, in our study a history of previous embolism was not significantly related to a thrombogenic milieu, although this parameter was shown in earlier anticoagulation trials to be an independent predictor for recurrent thromboembolism.
4–7 However, the rate of prior embolic events was relatively low in our patient population.
Another finding of our study was that multivariate analysis of risk factors showed that only age > 65 years and LVEF < 45% were independent predictors of a thrombogenic milieu. This finding supports the clinical risk stratification, with older patients and patients with heart failure having a higher risk of thromboembolism.4,5,23
Based on the data of the large anticoagulation trials patient groups of high or low risk for thromboembolic events have been defined (table 2).4,5 Our data confirm this risk stratification showing that a high risk identification according to either the SPAF III or the AFI criteria were strongly correlated to a thrombogenic milieu. Furthermore, moderate risk as defined by SPAF III criteria were also significantly associated with a thrombogenic milieu. The AFI classified all patients in age dependent risk categories with and without additional clinical risk factors (table 2). Their analysis of pooled data from five anticoagulation trials found an increasing thromboembolic event rate with higher patient age and in the presence of clinical risk factors. Our data show that older patients more often have a thrombogenic milieu than younger patients, confirming this risk stratification.
Another interesting finding of this study was that the number of risk factors in individual patients was significantly correlated to the probability of having a thrombogenic milieu. The presence of a single clinical risk factor was associated with a 46% incidence of a thrombogenic milieu. Furthermore, the number of risk factors was closely correlated to the presence of a thrombogenic milieu. Thus, our data imply that patients with one or more of the above mentioned clinical risk factors should be considered for chronic oral anticoagulation.
The most interesting finding of our study was that a group of patients presenting with AF without any verifiable clinical risk factor had either dense SEC or poor LAA flow velocities. Thus, there seems to be a certain subgroup of patients with an increased risk of thromboembolism who would be missed by clinical risk stratification. In light of the high probability of thromboembolism in patients with a thrombogenic milieu anticoagulation should be considered in these patients.
Study limitations
The number of patients in this study was relatively small. In future, larger trials including the collection of follow up data on embolic event rates will have to evaluate the cost effectiveness of routine TOE screening in patients with AF, as well as its contribution to decreasing the embolic event rate.
Conclusion and clinical implications
The TOE finding of a thrombogenic milieu and the presence of clinical risk factors are closely correlated. Thus, the results of the present study confirm the value of the clinical risk stratification proposed by the SPAF III trial and the results of the AFI group. The strongest predictors of a thrombogenic milieu as assessed by TOE are a reduced LVEF of < 45% and age > 65 years. Interestingly, there was a subgroup of patients presenting a thrombogenic milieu in the absence of any clinical risk factors. Thus, TOE may help to identify patients at risk for thromboembolism despite negative clinical risk factors. TOE risk stratification may be of particular value in patients where oral anticoagulation my be counterindicated or in younger patients without clinical risk factors.