Management of Atrial Fibrillation

Frequency and Pathogenesis

Nonvalvular atrial fibrillation (AF) is a potent predictor of first and recurrent stroke, affecting more than 2.7 million Americans. An estimated 14–38% of patients with ischemic stroke have AF . The frequency of ischemic stroke events in patients with AF is directly proportional to the mean age of populations studied. Of note, this data may be an underestimation due to the difficulty of detecting asymptomatic or paroxysmal AF . The presence of AF greatly increases the risk of ischemic stroke, and this effect is seen more prominently as age increases and in female populations . The prevalence of ischemic stroke associated with AF is less than 10% in patients under the age of 50, but rises to over 50% in patients above 90 years of age. In general, ischemic stroke patients with AF tend to be older, female, and have more comorbidities than patients with ischemic stroke without AF .

Patients with AF typically have more severe strokes as well as longer transient ischemic attacks (TIAs) than patients with ischemic stroke from other causes. Thus, strokes secondary to AF are generally associated with greater morbidity and mortality than strokes caused by other risk factors. Ischemic stroke caused by AF and cardioembolism carries a high mortality of 27.3%, compared with 21.7% for atherothrombotic strokes and 0.8% for lacunar infarcts. The higher impact of stroke associated with AF is believed to be related to cardioembolism as the primary mechanism . In general, emboli formed in cardiac chambers are larger than those produced by atherosclerotic plaques or other sources. The majority of ischemic strokes in patients with AF are due to embolism of thrombi that form within the left atrium, particularly the left atrial appendage (LAA). LAA thrombi in AF are precipitated by sluggish flow from ineffective atrial contraction. However, other factors also contribute to LAA thrombus formation, including associated cardiovascular disease, age, and hematologic factors . Further, an echocardiographic study indicated that LAA dysfunction can occur independently of the whole of the left atrium, suggesting a mechanism for the increased risk of ischemic stroke in paroxysmal AF .

It should be noted that cardioembolism does not account for all strokes in patients with AF. One study demonstrated that an estimated 70% of all strokes in patients with AF are secondary to cardioembolism, while the remaining 30% are composed of atherothrombotic and small vessel ischemic infarcts. This study highlights the fact that patients with AF often have several common comorbidities that may additionally contribute to the risk for stroke, such as chronic hypertension (HTN). HTN independently increases the risk for both ischemic and hemorrhage stroke. Ischemic strokes secondary to cardioembolism are also associated with a 71% rate of hemorrhagic conversion . With the variation in comorbidities in each patient, evaluating risk involves clinical judgment and referring to the current evidence and classification schemes. This is critical, as estimating an individual AF patient’s stroke risk is a key factor in determining an appropriate medication to prevent future stroke. As an example, a younger patient with lone AF does not have the same risk for future ischemic stroke or the same risk for developing bleeding complications as an elderly patient with several other comorbidities. Thus the management for these patients will differ.

The Role of Echocardiography in Estimating Stroke Risk

Echocardiography is helpful in assessing risk of stroke in patients with AF. Left ventricular dysfunction seen on echocardiography significantly increases ischemic stroke risk in both low-risk patients (0.4–9.3% per year) and high-risk patients (4.4–15% per year). Other important echocardiographic findings associated with an elevated thromboembolic risk include left atrial thrombus, LAA size, LAA peak velocity, and spontaneous echocardiographic contrast. Of these factors, left ventricular dysfunction and left atrial size appear to have the greatest predictive value for thromboembolism. Therefore, these characteristic echocardiographic findings may be helpful in stratifying patients and guiding management for stroke prevention .

Transesophageal echocardiography (TEE) may also be helpful in the evaluation of patients after ischemic stroke. In patients with comorbid atherosclerotic disease and AF, echocardiography combined with electrocardiography may be able to elucidate the specific source of ischemic stroke in such patients. In approximately 45% of patients, residual LAA thrombus may be seen. TEE may also identify a source in patients with suspected cardioembolic stroke without a definitive history of AF. TEE is more sensitive than transthoracic echocardiography (TTE) for detecting spontaneous echodensities and atrial appendage thrombi. If cardioversion is anticipated, TEE is essential to exclude the presence of thrombi prior to cardioversion .

Ischemic Stroke Risk Factors and Bleeding Risk

Among patients with nonvalvular AF, the annual ischemic stroke risk averages 3–4%. The absolute risk in an individual patient varies greatly based on the presence of risk factors. Although AF is considered an independent risk factor for stroke, this risk is relatively small when no comorbidities are present . However, several risk factors have been shown to escalate ischemic stroke risk in conjunction with AF ( Table 146.1 ). These risk factors include left ventricular systolic dysfunction or congestive heart failure, HTN, age >75 years, diabetes mellitus, previous stroke or TIA, vascular disease, and female sex. Of these factors, prior stroke or TIA and increasing age over 75 appear to be the most important. Vascular disease confers the smallest risk, with some studies not establishing a definitive correlation. Based on these factors, several risk stratification schemes have been developed. Two popular risk stratification models are the CHADS ₂ and the CHA ₂ DS ₂ -VASc. The CHADS ₂ does not include female sex and vascular disease. Both models try to take into account that the known risk factors for ischemic stroke in AF do not confer the same level of risk. Both CHADS ₂ and CHA ₂ DS ₂ -VASc assign two points to prior stroke/TIA, however CHA ₂ DS ₂ -VASc additionally takes into account increasing age, which also confers greater risk. The CHA ₂ DS ₂ -VASc tool is the currently recommended model for estimating risk in a patient with AF ( Table 146.2 ).

Risk stratification can guide clinical decision making and help determine the risk and benefit of treating a particular patient. Patients with CHA ₂ DS ₂ -VASc scores of 0 are considered to be low risk with an ischemic stroke risk of 0.2% per year. A CHA ₂ DS ₂ -VASc score of 1 is considered intermediate risk with an annual rate of 0.6%. CHA ₂ DS ₂ -VASc scores of 2 or greater are considered to be high risk with annual risk of ischemic stroke ranging from 2.2% to 12.2% ( Table 146.3 ).