Determining which strategy makes the most sense in obtaining normal sinus rhythm.
Atrial fibrillation (AF) is a common cardiac dysrhythmia encountered in the emergency department (ED), affecting 2.7 million to 6.1 million Americans annually. Hospitalizations with AF as the primary diagnosis total >467,000 annually. It is associated with a five-fold increased risk of ischemic stroke, a three-fold increase in risk of heart failure, and a two-fold increased risk of mortality.(1)
Previous studies comparing outcomes of rhythm-control using antiarrhythmics with rate-control in patients with AF failed to show a benefit of rhythm control on mortality.(2,3) However, for some patients, rhythm control improves symptoms and is associated with a better quality of life.(4) Given that up to 70% of AF terminates spontaneously within 24 hours, can a delayed or wait-and-see (WAS), approach to AF in the ED be adopted to avoid early cardioversion? (5)
Testing
RACE 7 ACWAS (Rate Control versus Electrical Cardioversion Trial 7 – Acute Cardioversion versus Wait and See) is a multi-center, randomized, non-inferiority trial, in 15 hospitals in the Netherlands to determine if a delayed cardioversion, or Wait-and-See (WAS) approach to hemodynamically stable, recent onset (<36hrs) AF in the ED has similar rates of conversion to sinus rhythm as early cardioversion at a four weeks post-ED visit.
ED patients were randomized in a1:1 ratio to either (a) early pharmacologic cardioversion, preferably with flecainide, or (b) delayed cardioversion (WAS). Patients were recruited over a four-year period at a variety of hospitals, including academic, non-academic teaching and nonteaching facilities. Transesophageal echocardiography prior to cardioversion was neither required nor performed in this study.
Patients in the WAS group had a target rate control to <110 bpm using IV or oral B-Blockers, non-dihydropyridine calcium channel blockers (diltiazem or verapamil), or digoxin. Patients were discharged home if clinically stable with an outpatient clinic visit and 12 lead ECG the next day (within 48 hours of symptom onset). Patients with persistent AF at the next-day follow-up were referred to the ED for delayed cardioversion.
Patients in the early cardioversion group who failed early pharmacologic cardioversion, or those with contraindications to pharmacologic cardioversion, or a history of previously unsuccessful pharmacologic cardioversion underwent electrical cardioversion. Those at high risk for stroke and not on previous anticoagulation were started on anticoagulants before or immediately after cardioversion. All patients had a four-week follow-up visit and 12 lead ECG to assess for presence or absence of AF.
Results
The primary outcome of the study was presence of sinus rhythm on ECG at the four-week follow-up visit.
Secondary outcomes included duration of the initial ED visit; number of ED visits related to AF; cardiovascular complications defined as events leading to an ED visit or hospital admission (including heart failure, ischemic stroke, TIA, unstable angina or ACS or hypotension); time until AF recurrence as determined via use of an ECG telemetry device (MyDiagnostick, Applied Biomedical Systems) or in case of symptoms, until the four-week visit. Patients’ quality of life using the Atrial Fibrillation Effect on Quality-of-Life questionnaire (AFEQT) was also gauged.
Patients included in the study were hemodynamically stable adults > 18-years-old with AF on ECG at a ventricular rate >70 bpm, for a duration <36 hours prior to presentation.
Exclusion criteria were hemodynamic instability, signs of MI on ECG, presence of pre-excitation syndrome, history of Sick Sinus Syndrome, history of unexplained syncope, history of persistent AF (AF lasting >48 hours), acute heart failure or other factors deemed unsuitable by the attending physician.
Of 437 patients who were randomized, 10 were lost to follow-up or withdrew consent. There were no significant differences in patient characteristics between the two groups at baseline. With regard to the primary outcome, 193/212 (91%) patients in the AWS group had NSR on ECG at the four-week follow-up. Similarly, the Early-Cardioversion group had 202/215 (94%) in NSR at the four-week mark. (95% CI -8.2 – 2.2; p = 0.005 for non-inferiority).
Amongst the WAS group, 150 (69%) were spontaneously in NSR at 48 hours and 61 (28%) required delayed chemical or electrical cardioversion. Rate control medication was given in 175 patients in the ED, consisting of metoprolol (82.9%), other beta blockers (5.7%) or verapamil (2.9%). In the Early Cardioversion group, 36 (16%) were spontaneously in NSR at 48 hours and 171 (78%) required early chemical or electrical cardioversion.
The median duration of the initial ED visit was 120 minutes for the AWS group and 158 minutes for the Early Cardioversion group.
Telemetric ECG recordings were available for 335 of 427 patients. Recurrence of AF occurred in 49/164 patients in WAS group (30%) with a median time of 12 days. Similarly, AF recurrence occurred in 50/171 patients in the early cardioversion group (29%) with a median time of eight days
There was no significant difference in the other secondary outcomes of cardiovascular complication rates, number of ED visits for AF, or mean AFEQT global scores between the two groups.
Rate-Control vs. Rhythm Control
This study supports previously known information and numbers regarding spontaneous conversion rates of AF to sinus rhythm. Reasons to pursue a rate-control strategy over rhythm control in the ED for the hemodynamically stable AF patient include avoiding complications of pharmaceutical cardioversion, avoiding need for sedation in electrical cardioversion, and decreased ED length of stay, particularly in light of the fact that the rate of spontaneous conversion to NSR has been reported up to 70%.
Patients in this Dutch study had access to close follow-up and reassessment within a day of their initial ED visit. This could prove to be a significant challenge and limiting step for many patients and providers in the U.S. In order to adopt this strategy, the ED provider would need to very carefully select a subset of patients who have been in AF for <36 hours and schedule a repeat visit within 48 hours of symptom onset to allow for cardioversion, if necessary. This would likely represent a small number of patients that would be eligible for this strategy.
Current guidelines recommend the use of anticoagulation in patients with a CHA2DS2-VASc score >2 in men or > 3 in women.(6) Pursuing a delayed cardioversion strategy on an outpatient basis for patients with AF in the ED at high risk for stroke would require calculation of the CHA2DS2-VASc score, discussion and initiation of anticoagulation prior to discharge home, to not only prevent stroke, but in anticipation of possible delayed cardioversion.
In this particular study 60 patients in the delayed conversion group were started on anticoagulants during the initial visit, the vast majority being direct oral anticoagulants (DOACs). Additionally, 90 patients in the delayed cardioversion group were already on some form of anticoagulation prior to their initial ED visit. With the recent update in guidelines to include DOACs for patients with AF, this strategy is made potentially easier.(6)
Of the WAS group, 125 patients had a history of recurrent AF while 120 of the early conversion group had a similar history. None had episodes lasting >48 hours. This means >50% of the patients in the study had a previous history of AF that terminated within 48 hours. Is a patient with a past history of spontaneously converting AF more likely to spontaneously convert to sinus rhythm again? If so, this would introduce an element of selection bias into the study and potentially inflate the rates of spontaneous conversion.
Conclusion
The long-term efficacy, safety and cost-effectiveness of a WAS approach compared to immediate cardioversion is still unknown. Fortunately, these are just the initial results of what is to be an eventual year-long study.
Knowing that most patients with AF will convert spontaneously to sinus rhythm and, in the absence of hemodynamic compromise, there is no need to rush for rhythm control in the ED. It is difficult to predict which specific patients will convert spontaneously and over what period of time. Providers need to assess severity and duration of symptoms, access to follow-up, risks for CVA, and available anticoagulation strategies, amongst other factors, in the management of patients with AF. Based on this study, a delayed conversion strategy for a specific group of AF patients demonstrates similar rates of sinus rhythm at four weeks with no difference in potential risks or patient-reported quality of life as compared to an early cardioversion strategy.
References:
- January CT et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation 2014. PMID: 24682348
- Olshansky B et al. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation. J Am Coll Cardiol 2004. PMID: 15063430
- Van Gelder IC et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002. PMID: 12466507
- Hagens VE et al. Effect of rate or rhythm control on quality of life in persistent atrial fibrillation: results from the Rate Control Versus Electrical Cardioversion (RACE) Study. J Am Coll Cardiol 2004. PMID: 14736444
- Pluymaekers NAHA et al. Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. N Engl J Med. 2019. PMID: 30883054
- January CT et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2019. PMID: 30703530
