Embolic risk and the role of anticoagulation in atrial flutter

INTRODUCTION — Most patients with atrial flutter should be considered for chronic anticoagulation in a manner similar to those with atrial fibrillation (AF). This recommendation is based not only on the fact atrial flutter carries a risk for systemic embolization but also that these patients usually have episodes of AF. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.)

Our approach to anticoagulation applies to all types of atrial flutter, whether it is typical or atypical. (See "Electrocardiographic and electrophysiologic features of atrial flutter".)

PREVALENCE OF THROMBUS — Many patients with atrial flutter have alternating periods of atrial fibrillation (AF) making it difficult to know the exact risk of thrombus formation (and subsequent embolization) specifically attributable to atrial flutter [1].

Atrial mechanical function is not normal in patients with atrial flutter. However, transmitral and left atrial appendage Doppler echocardiography commonly demonstrate more organized atrial and atrial appendage mechanical function with sustained atrial flutter, as opposed to AF, in which organized atrial contraction is absent. One study performed transesophageal echocardiography (TEE) immediately before and after cardioversion in 19 patients with atrial flutter and 44 patients with AF with the following findings [2]:

●Prior to cardioversion, patients with atrial flutter had greater left atrial appendage peak ejection velocities and shear rates compared to those with AF.

●After cardioversion, left atrial appendage peak ejection velocities and shear rates decreased in both groups of patients, but the impaired left atrial appendage function was less pronounced in patients with atrial flutter. New or increased spontaneous echo contrast, a marker of blood stasis, occurred significantly less often in patients with atrial flutter (21 versus 50 percent for AF).

●Like AF, the vast majority of thrombi among patients with atrial flutter are located in the left atrial appendage.

TEE evidence of atrial thrombi has been documented in a number of reports of patients with atrial flutter not receiving chronic anticoagulation [3-8]. As with AF, the thrombi overwhelmingly involve or are exclusively within the left atrial appendage. The frequency with which this occurs may vary with the duration of the arrhythmia and other risk factors (similar to AF) as illustrated by the following observations:

●Two series evaluated patients with atrial flutter for a mean duration of 33 to 36 days who did not have a history of AF, rheumatic heart disease, or a prosthetic heart valve [3,4]. A left atrial thrombus was found in 1 to 1.6 percent, a right atrial thrombus in 1 percent, and left atrial spontaneous echo contrast in 11 to 13 percent [3,4]. In one of these reports, there was a close correlation between a history of thromboembolism and periods of AF during atrial flutter [4].

●Atrial thrombi and spontaneous echo contrast may be more common in patients with atrial flutter of longer duration. In a TEE study of 30 patients with persistent atrial flutter (duration 6.4 months), two patients (7 percent) had thrombus in the left atrial appendage, and 25 percent had spontaneous echo contrast prior to cardioversion [5]. As described below in more depth (see 'Cardioversion' below) and mentioned above, left atrial contractile function (as measured by peak atrial appendage ejection velocity) transiently declines after cardioversion in many patients and is considered a manifestation of atrial "stunning."

●Left atrial thrombus was present in 5 of 47 consecutive patients (11 percent) with atrial flutter for a mean duration of 28 days who did not have a history of AF or mitral stenosis [6].

EMBOLIC RISK — The risk of embolization in atrial flutter is related to risk factors and the need for cardioversion or ablation.

Risk factors and lone atrial flutter — Risk factors for clinical thromboembolism include valvular heart disease (eg, rheumatic valve disease, prosthetic valves), increasing age, depressed left ventricular systolic function or heart failure, hypertension, diabetes, vascular disease, and a history of thromboembolism.

Atrial flutter without an identifiable risk factor is called lone atrial flutter. It is relatively uncommon, occurring in only 3 of 181 adults with atrial flutter in a population-based study (1.7 percent) [9] and in 8 percent of children and young adults with atrial flutter in a multicenter series [10].

The embolic risk associated with lone atrial flutter was evaluated in a review of 59 mostly elderly patients with lone atrial flutter (mean age at diagnosis 70 years); 75 percent developed recurrent episodes or persistent atrial flutter [11]. At presentation, these patients did not have coronary heart disease, hyperthyroidism, heart failure, valvular heart disease, congenital heart disease, obstructive lung disease, uncontrolled hypertension, or known antecedent atrial fibrillation (AF). At the time of diagnosis, 25 were treated with aspirin and six with warfarin; at last follow-up, 28 were treated with aspirin and 13 with warfarin.

The following observations were noted at an average follow-up of 10 years:

AF developed in 33 patients (56 percent), which was paroxysmal in 25 and permanent in eight, highlighting the rationale for managing anticoagulation in patients with atrial flutter in a manner similar to AF.

●One or more ischemic cerebrovascular events occurred in 19 patients (32 percent) at a mean age of 80 years, including six who were in AF at the time of the event. Compared to age- and sex-adjusted expected rates of thromboembolism, the thromboembolic risk was significantly increased in the patients with lone atrial flutter (hazard ratio 5.2 in patients with controlled hypertension and 2.5 in patients without a history of hypertension).

When compared with patients with lone AF, the patients with lone atrial flutter had, after adjustment for age and sex, a significantly higher rate of thromboembolism (hazard ratio 2.6). The risk was lower and no longer significant when only patients without a history of hypertension were included (hazard ratio 1.9). (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.)

Long-term flutter — There is an increased risk for clinical thromboembolism in patients with persistent atrial flutter compared to the general population without atrial arrhythmias [1,12-14]. In a systematic review based upon limited data, the long-term embolic risk in patients with sustained atrial flutter (with varying risk factors) was estimated to be approximately 3 percent per year [12]. For comparison, the rate of thromboembolism in patients with AF <1 percent per year in patients with no risk factors, with the rate increasing with increasing CHA₂DS₂-VASc score (table 1).

One problem with interpreting these data, as mentioned previously, is that many patients with persistent atrial flutter also have episodes of AF (34 percent in the preceding report [13]) also have episodes of AF. In a review of the Medicare database, the risk of stroke was significantly increased in patients with atrial flutter (relative risk 1.41 compared to a control group). In these patients, the relative risk was 1.56 in patients who subsequently had an episode of AF (similar to the risk with AF alone), while those with isolated atrial flutter had a stroke risk not significantly different from the control population (relative risk 1.11) (figure 1) [1].

Cardioversion — Although the risk of clinical thromboembolization at the time of cardioversion is increased compared to individuals not undergoing cardioversion, the absolute thromboembolism risk of cardioversion for pure atrial flutter is not known with a high degree of confidence due to the fact that many patients included in reports of atrial flutter cardioversion related events also had episodes of AF (but happened to be in atrial flutter at the time of cardioversion) [3,13,15-17].

The studies that have attempted to evaluate the risk at the time of cardioversion studied different populations. Some included patients with a prior history of thromboembolism and were thus more likely to report high event rates, while studies in which at least some patients were anticoagulated or underwent precardioversion transesophageal echocardiography (TEE) to assess for thrombus were more likely to report low event rates [3,12-17].

Three early studies found no embolic events in a total of 314 patients with atrial flutter (and without AF) who underwent elective cardioversion for atrial flutter without anticoagulation prior to or after cardioversion [4,18,19]. However, the overall incidence is 0.6 to 1.0 percent [16,17] with a higher risk in patients with a history of AF or underlying heart disease [13,15]. In a meta-analysis of these studies, the rate of short-term emboli ranged from 0 to 7.3 percent [12].

Embolization may be related to a transient reduction in atrial mechanical function leading to post-cardioversion thrombus formation, referred to as atrial "stunning," and is present after successful cardioversion of atrial flutter [2,5,6,20,21]. In one report, left atrial appendage peak ejection velocity fell by 26 percent within 15 minutes of cardioversion and almost 50 percent of subjects had new or more pronounced spontaneous echo contrast [5]. These changes predispose to de novo thrombus formation [15]. Similar observations have been made in patients with AF. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Atrial stunning'.)

The severity of atrial stunning appears to be somewhat less pronounced in atrial flutter than in AF, which could explain the lower embolic risk after cardioversion in atrial flutter. In a report that compared 19 patients with atrial flutter with 44 patients with AF, the left atrial appendage peak ejection velocity was significantly higher in the patients with atrial flutter at baseline (42 versus 28 cm/sec in atrial fibrillation) and after cardioversion (27 versus 15 cm/sec) [2]. In addition, new or more pronounced spontaneous echo contrast was significantly less likely in those with atrial flutter (21 versus 50 percent).

Radiofrequency catheter ablation — Atrial stunning (see 'Cardioversion' above) also occurs after radiofrequency catheter ablation [21,22]. The likelihood of developing atrial stunning and its duration were assessed in a review of 15 patients with persistent atrial flutter (mean duration 17 months) and seven with paroxysmal atrial flutter who underwent radiofrequency catheter ablation [21]. Significant left atrial appendage stunning and spontaneous echo contrast on TEE were observed after ablation in 80 percent of those with persistent flutter but in none with paroxysmal atrial flutter, suggesting that, like AF, left atrial stunning in atrial flutter is related to the duration of the arrhythmia and not the mode of reversion. These changes resolved after three weeks of sustained sinus rhythm. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'RF catheter ablation'.)

PREVENTION OF EMBOLIZATION

Patients with long-term atrial flutter — Patients with persistent or recurrent atrial flutter who also have periods of atrial flutter-fibrillation should be treated in the same manner as those with pure atrial fibrillation (AF) [23,24]. This recommendation also applies to patients with atrial flutter who have a prior history of AF. Though the optimal management of atrial flutter without any history of AF is uncertain and may be more limited (figure 1) [1], we and others recommend that patients with pure atrial flutter be managed similar to those with AF [25]. (See "Atrial fibrillation in adults: Use of oral anticoagulants", section on 'Summary and recommendations'.)

Anticoagulation with warfarin (goal international normalized ratio [INR] between 2.0 and 3.0) has been recommended to prevent embolization in patients with atrial flutter, similar to patients with AF (eg, using CHA₂DS₂-VASc criteria for nonvalvular AF). Of the non-vitamin K oral anticoagulants tested for stroke prevention in AF, in the large clinical trials, only apixaban enrolled patients with atrial flutter [26]. It is likely, however, that there is similar efficacy of all the non-vitamin K oral anticoagulants (eg, apixaban, dabigatran, edoxaban, and rivaroxaban) for atrial flutter as well as AF.

At the time of cardioversion — We and others recommend that anticoagulation leading to, at the time of, and after cardioversion of atrial flutter be managed in a manner similar to that for AF [23,24]. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".)

Patients presenting with an initial episode of atrial flutter should be treated in a manner similar to those presenting with their first episode of AF, including a transthoracic echocardiogram (TTE) to evaluate for congenital heart disease, valve disease, and left ventricular systolic function.

After radiofrequency catheter ablation — Anticoagulation recommendations following catheter ablation of AF are discussed separately. (See "Atrial flutter: Maintenance of sinus rhythm", section on 'Anticoagulation after RF catheter ablation'.)

RECOMMENDATIONS OF OTHERS — The 2016 European Society of Cardiology guidelines for the management of atrial fibrillation, the 2015 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline on the management of adult patient with supraventricular tachycardia, and the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline on the management of patients with atrial fibrillation (and its 2019 focused update) similarly recommend managing anticoagulation in patients with atrial flutter in a manner similar to those in atrial fibrillation [23,27-31], recognizing that no report has been sufficiently large to accurately define both the risk of embolization and benefit of antithrombotic therapy in a pure atrial flutter population.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".)

SUMMARY AND RECOMMENDATIONS

●The risk of embolization in atrial flutter is related to clinical risk factors and underlying cardiac disease (eg, valve disease). However, the exact rates are not known, in part due to the presence of atrial fibrillation (AF) in most cohorts studied and the coexistence of AF and atrial flutter in most individuals. (See 'Long-term flutter' above.)

●For patients with atrial flutter, with or without AF, we recommend an anticoagulant strategy identical to that used in patients with AF (Grade 1B). (See 'Prevention of embolization' above.)