Atrial Flutter and Thromboembolic Risk: A Systematic Review
In this systematic review, we provide estimates of the TE risks associated with atrial flutter. Notwithstanding the limitations of observational and indirect data from echocardiographic studies, this systematic review confirms that clinical TE, left atrial thrombus and SEC are highly prevalent in atrial flutter. A clear increase in TE risk is evident with this arrhythmia; however, due to large heterogeneity it is not possible to make an exact estimate of this risk (Table 1 and Table 2).
The risk of stroke and TE associated with atrial flutter is unlikely to be homogeneous and is dependent upon the presence of additional stroke risk factors. These risk factors predispose to the development of atrial flutter, and in addition, contribute to TE risk. It is well known that patients with atrial flutter frequently have AF and it has also been proposed that atrial flutter and AF are dependent on each other.
In 2001, ACC/AHA/ESC published the first international guidelines on the management of AF where the management of atrial flutter was briefly described. The guidelines state that antithrombotic therapy for patients with atrial flutter, in general, should be as for those with AF. This recommendation was based on echocardiographic studies showing that the emptying of the left atrial appendage is decreased during atrial flutter compared with sinus rhythm, but higher than in AF. In addition, there is a transient mechanical dysfunction (stunning) of the left atrium and left atrial appendage after successful ablation or DCC of atrial flutter. The guidelines acknowledge that RCTs of antithrombotic therapy in the treatment of atrial flutter were lacking, but emphasised that in case–control series the risk for TE is 1%–5%. The guidelines state that the risk of thromboembolism for patients with chronic atrial flutter is generally estimated higher than for patients with sinus rhythm, but less than for those with persistent or permanent AF. In 2003, the ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias was published, emphasising that the knowledge about the TE risk associated with atrial flutter was limited, being based upon observational and echocardiographic studies and recommended that anticoagulant treatments in patients with AF should be extended to those with atrial flutter. In subsequent ACC/AHA/ESC guidelines from 2006, 2008, 2010, 2011 and 2013, the recommendation 'Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF' with a level of evidence C is maintained.
There were five studies reporting TEE finding and TE events. Three studies found no relationship between SEC and TE events. Irani et al found 11 patients with positive SEC and one patient suffered an undefined cerebrovascular accident 4 days after TEE and start of anticoagulant treatment. Seidl et al performed TEE examination in 44 patients with a prior TE event or expected higher risk of TE. They found SEC in seven patients; however, it is not reported if these patients underwent cardioversion or ablation or whether there were a TE event in this group. However, as the relationship between SEC and TE events are debateable, these data could not identify a clear consistency between these.
In 1998, Berger and Schweitzer published a review of articles published between 1966 and 1997, included 32 studies with 4621 patients who underwent cardioversion for atrial flutter and AF: 92 (2%) patients had a TE event after cardioversion but the results do not discriminate between the underlying arrhythmias. Moreyra et al also reviewed the risk of TE events related to cardioversion from pooled results in seven TEE-guided trials compared with 18 historical controlled trials with 'blind' cardioversion in both anticoagulant and non-anticoagulant patients, with atrial flutter being present in 10.6% in the TEE studies and 9% in control studies. The results were not clearly stratified for atrial flutter and AF and the reported TE events rate were 1.34% (TEE group), 0.33% (control group anticoagulant) and 2% (control group non-anticoagulant). However in the study by Bertaglia et al, there were no TE events after cardioversion of patients with atrial flutter, despite that 56% had hypertension and 30% ischaemic heart disease and thereby a minimum CHA2DS2-VASc above one. Additionally, Clementy et al demonstrated an improve survival rate independent of coexisting AF when undergoing atrial flutter ablation. However, the use of anticoagulation was not well balanced between control and cases (55% vs 74%), and the patient population in general had a high risk of stroke as reflected by a CHA2DS2-VASc score above three in both groups. In 2005, Ghali et al published a systematic review and meta-analysis on atrial flutter and the risk of TE. They included 13 studies investigating the risk of TE in relation to cardioversion and four studies reporting the long-term TE risks of atrial flutter. They concluded that the reported risk of thromboembolism around the time of cardioversion for atrial flutter varied by study, and that study-level clinical factors contributed to the variability in reported event rates. Nonetheless, Ghali et al suggested that the risk of thromboembolism was indeed elevated as compared with patients in sinus rhythm.
It is possible that our inclusion criteria excluding foreign language papers could have led to some selection bias. There was marked heterogeneity and low-quality data highlighting the differences in the endpoints employed, differing follow-up periods, clinical and methodological differences and other confounding factors, which should be taken into consideration when interpreting the findings. Due to the close relationship between atrial flutter and AF, the presence of AF may be underestimated in the included studies, and furthermore it was not possible to determine the type of atrial flutter (typical, atypical, etc). Additionally, it cannot be ruled out that some of the available data from atrial flutter populations do not include patients with silent AF. The inclusion of patients with rheumatic heart disease may overestimate the TE risk, as patients with rheumatic heart disease per se carry a higher TE risk. Lastly, the 'true' TE risk may be underestimated because the included studies mainly focused on stroke and/or TIA and did not report on systemic embolism.
Discussion
In this systematic review, we provide estimates of the TE risks associated with atrial flutter. Notwithstanding the limitations of observational and indirect data from echocardiographic studies, this systematic review confirms that clinical TE, left atrial thrombus and SEC are highly prevalent in atrial flutter. A clear increase in TE risk is evident with this arrhythmia; however, due to large heterogeneity it is not possible to make an exact estimate of this risk (Table 1 and Table 2).
The risk of stroke and TE associated with atrial flutter is unlikely to be homogeneous and is dependent upon the presence of additional stroke risk factors. These risk factors predispose to the development of atrial flutter, and in addition, contribute to TE risk. It is well known that patients with atrial flutter frequently have AF and it has also been proposed that atrial flutter and AF are dependent on each other.
In 2001, ACC/AHA/ESC published the first international guidelines on the management of AF where the management of atrial flutter was briefly described. The guidelines state that antithrombotic therapy for patients with atrial flutter, in general, should be as for those with AF. This recommendation was based on echocardiographic studies showing that the emptying of the left atrial appendage is decreased during atrial flutter compared with sinus rhythm, but higher than in AF. In addition, there is a transient mechanical dysfunction (stunning) of the left atrium and left atrial appendage after successful ablation or DCC of atrial flutter. The guidelines acknowledge that RCTs of antithrombotic therapy in the treatment of atrial flutter were lacking, but emphasised that in case–control series the risk for TE is 1%–5%. The guidelines state that the risk of thromboembolism for patients with chronic atrial flutter is generally estimated higher than for patients with sinus rhythm, but less than for those with persistent or permanent AF. In 2003, the ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias was published, emphasising that the knowledge about the TE risk associated with atrial flutter was limited, being based upon observational and echocardiographic studies and recommended that anticoagulant treatments in patients with AF should be extended to those with atrial flutter. In subsequent ACC/AHA/ESC guidelines from 2006, 2008, 2010, 2011 and 2013, the recommendation 'Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF' with a level of evidence C is maintained.
There were five studies reporting TEE finding and TE events. Three studies found no relationship between SEC and TE events. Irani et al found 11 patients with positive SEC and one patient suffered an undefined cerebrovascular accident 4 days after TEE and start of anticoagulant treatment. Seidl et al performed TEE examination in 44 patients with a prior TE event or expected higher risk of TE. They found SEC in seven patients; however, it is not reported if these patients underwent cardioversion or ablation or whether there were a TE event in this group. However, as the relationship between SEC and TE events are debateable, these data could not identify a clear consistency between these.
In 1998, Berger and Schweitzer published a review of articles published between 1966 and 1997, included 32 studies with 4621 patients who underwent cardioversion for atrial flutter and AF: 92 (2%) patients had a TE event after cardioversion but the results do not discriminate between the underlying arrhythmias. Moreyra et al also reviewed the risk of TE events related to cardioversion from pooled results in seven TEE-guided trials compared with 18 historical controlled trials with 'blind' cardioversion in both anticoagulant and non-anticoagulant patients, with atrial flutter being present in 10.6% in the TEE studies and 9% in control studies. The results were not clearly stratified for atrial flutter and AF and the reported TE events rate were 1.34% (TEE group), 0.33% (control group anticoagulant) and 2% (control group non-anticoagulant). However in the study by Bertaglia et al, there were no TE events after cardioversion of patients with atrial flutter, despite that 56% had hypertension and 30% ischaemic heart disease and thereby a minimum CHA2DS2-VASc above one. Additionally, Clementy et al demonstrated an improve survival rate independent of coexisting AF when undergoing atrial flutter ablation. However, the use of anticoagulation was not well balanced between control and cases (55% vs 74%), and the patient population in general had a high risk of stroke as reflected by a CHA2DS2-VASc score above three in both groups. In 2005, Ghali et al published a systematic review and meta-analysis on atrial flutter and the risk of TE. They included 13 studies investigating the risk of TE in relation to cardioversion and four studies reporting the long-term TE risks of atrial flutter. They concluded that the reported risk of thromboembolism around the time of cardioversion for atrial flutter varied by study, and that study-level clinical factors contributed to the variability in reported event rates. Nonetheless, Ghali et al suggested that the risk of thromboembolism was indeed elevated as compared with patients in sinus rhythm.
Limitations
It is possible that our inclusion criteria excluding foreign language papers could have led to some selection bias. There was marked heterogeneity and low-quality data highlighting the differences in the endpoints employed, differing follow-up periods, clinical and methodological differences and other confounding factors, which should be taken into consideration when interpreting the findings. Due to the close relationship between atrial flutter and AF, the presence of AF may be underestimated in the included studies, and furthermore it was not possible to determine the type of atrial flutter (typical, atypical, etc). Additionally, it cannot be ruled out that some of the available data from atrial flutter populations do not include patients with silent AF. The inclusion of patients with rheumatic heart disease may overestimate the TE risk, as patients with rheumatic heart disease per se carry a higher TE risk. Lastly, the 'true' TE risk may be underestimated because the included studies mainly focused on stroke and/or TIA and did not report on systemic embolism.