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Cardioversion of Atrial Fibrillation and Atrial Flutter Revisited: Current Evidence and Practical Guidance For A Common Procedure
Cardioversion of Atrial Fibrillation and Atrial Flutter Revisited: Current Evidence and Practical Guidance For A Common Procedure
Cardioversion of Atrial Fibrillation and Atrial Flutter Revisited: Current Evidence and Practical Guidance For A Common Procedure
doi:10.1093/europace/euaa057
Received 30 October 2019; editorial decision 19 February 2020; accepted 25 February 2020; online publish-ahead-of-print 26 April 2020
Cardioversion is widely used in patients with atrial fibrillation (AF) and atrial flutter when a rhythm control strategy is pursued. We sought
to summarize the current evidence on this important area of clinical management of patients with AF including electrical and pharmaco-
logical cardioversion, peri-procedural anticoagulation and thromboembolic complications, success rate, and risk factors for recurrence to
give practical guidance.
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Key points
• Electrical cardioversion terminates AF in over 90% of cases
and is the treatment of choice in haemodynamically compro-
mised patients.
• Pharmacological cardioversion mainly converts recent-onset
AF of <48 h duration.
• Electrical cardioversion with an antero-posterior electrode po-
sition restores sinus rhythm better than with an antero-apical
position.
• Complications of ECV and PCV are generally rare.
relapse gap can be reached. The relapse gap may be lengthened by all
Table 1 Major complications of PCV and ECV in 1801
AADs but notably also by intracellular calcium-lowering drugs includ-
real-world patients from the Euro Heart Survey
ing verapamil and beta-blockers as well as angiotensin receptor
PCV (n 5 1089), ECV (n 5 712), blockers.19 Later (sub-acute) recurrences are prevented by all AADs
N (%) N (%) but even better if combined with an angiotensin receptor blocker or
.................................................................................................
verapamil.25,26 Beta-blockers alone may also reduce sub-acute recur-
Non-sudden cardiac death 1 (0.1) 2 (0.3)
rences.27 Presumably, these (add-on) agents control intracellular cal-
Sick sinus syndrome 5 (0.5) 5 (0.7)
cium overflow in atrial cells not used to large calcium transients after
Ventricular tachycardia 2 (0.2) 6 (0.8)
having been in AF for months. Late re-occurrences (Figure 2) respond
Torsades de pointes 3 (0.3) 1 (0.1)
well to AADs and may be managed by season-ticket-ECV, i.e. repeat
Ventricular fibrillation 0 3 (0.4)
single ECVs, in patients with low risk of recurrence.23,28 However, if
Asystole 7 (0.7) 2 (0.3)
recurrence risk is high, catheter ablation is the preferred option.1,29
Cardiac syncope 8 (0.8) 1 (0.1)
Key points
• Predictors of successful ECV of persistent AF are AF duration,
patient age, better function class, and pre-treatment with
AADs.
sotalol administered orally for 1 month is associated with a modest Although this pharmacological effect seems modest, it could be useful
conversion rate around 25%.28 Also, chronic administration of flecai- when temporary AAD therapy prior to ECV is considered.23,30
nide and propafenone may convert persistent AF but—as a side ef- Notwithstanding the above, recent-onset or paroxysmal AF
fect—may cause fast ventricular rates during ongoing AF.39,40 may terminate spontaneously (Figure 3). Antiarrhythmic drugs fore-
Verapamil may enhance chronic drug conversion with amiodarone.41 shorten time to sinus rhythm but at the end of the day, numbers of
patients in sinus rhythm are the same.5,10
A risk-based approach to choosing long-term rhythm control ther-
apy after cardioversion (no therapy, AADs, catheter ablation, or
Table 2 Drugs affecting cardioversion by lowering ECV combination of these two treatments) is desirable. Prediction models
threshold or suppressing IRAF
for recurrent AF are being developed and will need to be based on
Decrease threshold for Suppress sub-acute representative, combined data sets.42
cardioversion recurrences
or suppress IRAF
100
80
% of patients in sinus rhythm
Propafenone
Flecainide
60
Amiodarone
40
All non-AAD drugs
20
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Figure 3 Conversion to sinus rhythm over time after start of drug therapy for recent-onset AF. Class Ic AADs foreshorten time to sinus rhythm
significantly. Amiodarone and non-AAD (rate control drugs) are associated with spontaneous conversion, with minimal conversion action of amio-
darone discernable from 6 h on. At the end of the day around 60–70% of patients reached sinus rhythm. Modified after Crijns et al.,10 with permission.
AAD, antiarrhythmic drug; AF, atrial fibrillation.
Cardioversion of AF and AFL revisited 1153
20
Key points 15
15
• Electrical cardioversion and PCV carry the same thromboem-
bolic risk. 10
• Cardioversion of AF and AFL carry the same thromboembolic 4 3 3 3
5
risk. 1 1 1 1
0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
existing thrombi, transient atrial stunning after cardioversion, changes reduced LAA flow velocities, is the cardiac factor most strongly asso-
in mechanical atrial systolic function, left atrial size, and a prothrom- ciated with LAA thrombus and embolic events.70 Accordingly, the
botic state.58 presence of low flow velocities and/or SEC requires meticulous eval-
uation of the LAA before cardioversion. In addition to SEC and low
LAA flow velocities, TOE may also help identifying other predictors
Key points of thromboembolism, e.g. complex aortic plaques. An algorithm de-
• Almost all thromboembolic events with cardioversion occur
tailing echocardiographic evaluation of LAA prior to cardioversion
within 10 days after the procedure.
has previously been provided (Figure 5).63
• Therefore, anticoagulation up to 4 weeks after cardioversion is
recommended.
Key points
• A left atrial thrombus is observed in about 10% of non-valvular
Image-guided cardioversion AF.
LAA Thrombus
present
No Yes
Doppler evaluation of No
LAA velocities: > 40 cm/s
Yes
Safe to perform
cardioversiona
Figure 5 Schematic approach for the TOE evaluation of the LAA before cardioversion. From Beigel et al.,63 with permission. aSafe if no other con-
traindications exist for the patient. TOE refers to 2D TOE, but 3D TOE should be used, if available, to increase sensitivity and specificity of findings.
2D, 2-dimensional; 3D, 3-dimensional; LAA, left atrial appendage; TOE, transoesophageal echocardiography.
0.99 and 0.94 vs. TOE with significantly improved specificity of the as a conventional cardioversion strategy with at least 3 weeks of
delayed imaging protocols. Cardiac magnetic resonance demon- OAC pre-treatment in terms of thromboembolic events and bleed-
strated sensitivity and specificity of 0.80 and 0.98 when compared ing.85–88 In the ACUTE (Assessment of Cardioversion Using
with TOE. There was no significant difference in the sensitivity or Transesophageal Echocardiography) Study, the rate of haemorrhagic
specificity between MDCT and CMR. events was even significantly lower in the TOE-guided cardioversion
group. On the other hand, the TOE-group showed a numerical trend
Transoesophageal echocardiography- towards more deaths.85 While some studies show greater rates of
guided cardioversion successful restoration of sinus rhythm with TOE-guided cardiover-
Current guidelines recommend TOE to exclude intra-cardiac sion,85,86 inconsistent results exist as to long-term maintenance of si-
thrombi, if a strategy of early cardioversion without being therapeuti- nus rhythm.85,89
cally anticoagulated the preceding 3 weeks is pursued in patients who
have been in AF for >48 h.1,83 Oral anticoagulation treatment should
Key points
be initiated immediately in all patients scheduled for cardioversion • When no LA thrombus is identified on TOE, cardioversion
and maintained for at least 4 weeks. Long-term OAC treatment is
can be performed safely, provided that sufficient anticoagula-
based on the thromboembolic risk profile of the individual patient
tion is achieved before TOE.
and should be assessed using the CHA2DS2-VASc score.1,83
Cardioversion can be performed safely, if no LA thrombus is identi-
fied, provided that sufficient anticoagulation is achieved before
TOE.83 Thus, timing of cardioversion in relation to initiation of antico-
agulant therapy is crucial and should depend on the pharmacokinetics Studies comparing cardioversion
of the drug chosen, as the procedure should be performed under on non-vitamin K oral
therapeutic anticoagulation. If a thrombus is identified on TOE, ap-
propriate anticoagulation is recommended for at least 3 weeks, be- anticoagulant vs. vitamin K
fore a repeat TOE is done to ensure thrombus resolution.84 antagonist and special subgroups
Several randomized and observational studies investigating both
low-molecular-weight heparin (LMWH)/warfarin and different Since the first NOAC became available for stroke prevention in AF in
NOACs have demonstrated that TOE-guided cardioversion is as safe Europe in 2011, their use has been rapidly increasing.90–92 A similar
1156 A. Brandes et al.
Table 3 Large studies investigating NOACs vs. VKA in the cardioversion setting
Study (year) RE-LY (2011)96 X-VeRT (2014)87 ENSURE-AF (2016)88 EMANATE (2018)100
undefined undefined undefined undefined
....................................................................................................................................................................................................................
Study type Multicentre, international, Multinational, randomized, Multicentre, prospective, ran- Multinational, prospective,
post hoc analysis open-label, parallel-group domized, open-label, paral- randomized, open-label
Phase IIIb study lel-group with blinded with blinded endpoint
endpoint adjudication
NOAC Dabigatran Rivaroxaban Edoxaban Apixaban
Total number of patients 1270 (1319/664)a 1504 (1002/502) 2199 (1095/1104) 1500 (753/747)
(NOAC/warfarin) (N)
Follow-up 30 days 30 days 58 days 30 days (90 days in patients
b.i.d., twice a day; CHA2DS2-VASc, Congestive heart failure, Hypertension, Age >_75 years, Diabetes mellitus, Stroke, Vascular disease, Age 65–74 years, Sex category (female);
CRNM bleeds, clinically relevant non-major bleeds; EMANATE, Eliquis evaluated in acute cardioversion compared to usual treatments for anticoagulation in subjects with atrial
fibrillation; ENSURE-AF, edoxaban vs. warfarin in subjects undergoing cardioversion of atrial fibrillation; MI, myocardial infarction; N/R, not reported; NOAC, non-vitamin K
oral anticoagulant; o.d., once daily; RE-LY, Randomized Evaluation of Long-Term Anticoagulation Therapy; TIA, transient ischaemic attack; TOE, transoesophageal echocardiog-
raphy; TTR, time in therapeutic range; VKA, vitamin K antagonist; X-VeRT, explore the efficacy and safety of once-daily oral rivaroxaban for the prevention of cardiovascular
events in patients with non-valvular atrial fibrillation scheduled for cardioversion.
a
Total number of cardioversions.
b
15 mg o.d. in patients with CrCL of 30–49 mL/min.
c
30 mg o.d., if CrCl 15–50 mL/min, body weight <_60 kg or use of P-gp inhibitors.
d
2.5 mg b.i.d., if at least two of the following: age >_80 years, weight <_60 kg, or serum creatinine >_1.5 mg/dL (>_133 mmol/L). Cardioversion could be performed 2 h after a loading
dose of 10 mg (5 mg, if at least two of the following: age >_80 years, weight <_60 kg, or serum creatinine >_1.5 mg/dL [>_133 mmol/L]).
e
From main study.
1158 A. Brandes et al.
Cardioversion in patients with atrial structured clinical follow-up is mandatory to recognize AF recur-
fibrillation after acute coronary rences, to ensure appropriate and effective rhythm control therapy,
to evaluate symptoms, and to optimize treatment of underlying car-
syndrome and/or percutaneous coronary diovascular conditions.
intervention
Atrial fibrillation and coronary artery disease commonly coexist,113 Conflict of interest: A.B. has received lecture fees from Bayer,
and 5–10% of patients undergoing percutaneous coronary inter- Boehringer-Ingelheim, Bristol-Myers Squibb, MSD; and research sup-
vention (PCI) also have AF.114 Therefore, the vast majority of these port from Gilead, the Region of Southern Denmark, and the Zealand
patients require combination therapy with OACs and antiplatelet Region. E.L.G. has received speaker honoraria or consultancy fees
drugs for a limited period of time after the procedure.115 Acute car- from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers
dioversion can be justified in patients who are haemodynamically un- Squibb, Pfizer, MSD, Portola Pharmaceuticals, and Roche. He is an in-
stable, but usually cardioversion can be deferred. If a cardioversion is vestigator in the THEMIS, SATELLITE, and FLAVOUR studies
planned during the chronic phase after PCI, while patients are on (AstraZeneca) and has received research grants from Boehringer
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