Special Report
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Catheter ablation for asymptomatic atrial fibrillation? Expert Rev. Cardiovasc. Ther. Early online, 1–6 (2015)
Simon Kochha¨user and Atul Verma* Southlake Regional Health Centre, 602-581 Davis Dr, Newmarket, Ontario L3Y 2P6, Canada *Author for correspondence: Tel.: +1 905 953 7917 Fax: +1 905 953 0046 [email protected]
Ablation therapy for atrial fibrillation (AF) has been shown to be more efficient than medical treatment alone. Long-term success of AF ablation is still around 50% after one ablation and higher after two, with a substantial amount of asymptomatic recurrences in formerly symptomatic patients. Given the lack of evidence for superiority of rhythm control over rate control in terms of stroke reduction and mortality, AF ablation remains a treatment for symptom reduction only, although ablation has never been a part of these studies. There is early evidence that ablation could decrease the long-term risk of stroke; however, prospective studies are needed to assess whether this is the case and how patients with a successful ablation can be identified. If AF ablation can be shown to improve long-term morbidity, it could also become a reasonable treatment for patients with asymptomatic AF. KEYWORDS: ablation . anticoagulation . atrial fibrillation . outcome . stroke
Atrial fibrillation (AF) is one of the most common arrhythmic disorders with an increasing prevalence in older people [1,2]. Considering current demographic trends, the impact of AF on health care systems is expected to be increasingly burdensome [3]. AF is a progressive disease that often begins in a paroxysmal pattern and progresses to persistent AF with longer and more frequent episodes. AF significantly contributes to morbidity and mortality by causing symptoms such as fatigue, palpitations and shortness of breath in varying severity and also increasing the risk of stroke, neurodegenerative disease and even death [2,4–8]. There are two main therapy strategies in the treatment of AF. One is rate control, which aims to keep the resting heart rate at less than 100 bpm [9,10]. Rhythm control includes rate control but also attempts to restore and maintain sinus rhythm as often and for as long as possible. The first-line treatment for rhythm control is the use of antiarrhythmic drugs to suppress AF and prevent its progression. The discovery of focal activity generated from the pulmonary veins (PV) as a key trigger of AF [11] introduced electrical isolation of the PVs by catheter ablation as an interventional therapy for AF. Several studies have showed that PV isolation is an effective informahealthcare.com
10.1586/14779072.2015.1011128
tool for reducing AF burden and symptoms in formerly symptomatic patients [12–15] and is often more effective in reducing AF recurrence than antiarrhythmic drugs [12,16–18]. This is true for patients with paroxysmal and persistent AF, although success rates are significantly lower in persistent AF [14,16]. Despite its efficacy, ablation has never been shown to reduce stroke or mortality. In fact, older trials comparing rate control with rhythm control showed no benefit of the latter and perhaps a trend toward increased stroke [19,20]. Although generally more efficient at preventing AF recurrence compared to drug treatment, as an invasive treatment, ablation carries important and serious complications that remain at 1–2% [21,22]. Another advantage of drug therapy, not to be underestimated nowadays, is the lower short-term cost when compared to the fairly elaborate procedure of AF ablation. For these reasons, ablation has remained a therapy for improvement of quality of life in symptomatic patients (FIGURE 1) [13,16,23]. Following the current guideline recommendations, experience on the efficacy and safety of AF ablation in asymptomatic patients is scarce. A substudy of a prospective Italian registry showed that AF recurrence and complication rates were comparable between patients
2015 Informa UK Ltd
ISSN 1477-9072
1
Special Report
¨ user & Verma Kochha
Algorithm for rate vs rhythm control for patients with symptomatic AF Symptomatic AF
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Special circumstances in which to consider early rhythm control: • Highly symptomatic • Multiple recurrences • Extreme impairment in QOL • Arrhythmia-induced cardiomyopathy
Attempt rate control: β-blocker Calcium channel blocker
Symptoms resolve
Yes
Continue rate control
No Modify rate control consider rhythm control Paroxysmal AF High burden recurrence
Low burden recurrence Pill in pocket anti-arrhythmic therapy
Persistent AF
Maintenance anti-arrhythmic therapy
Consider cardioversion
Symptoms improve, but AF recurs
Catheter ablation
Symptoms improve, and patient maintains sinus rhythm
Symptoms do not change in sinus rhythm and AF recurs
Observe, if AF recurs, determine if symptomatic
Figure 1. Decision algorithm for rate or rhythm control in patients with symptomatic atrial fibrillation. Reprinted from the “2014 focused update of the Canadian Cardiovascular Society guidelines for the management of atrial fibrillation” [26] with permission from Elsevier.
with and without symptoms [24]; however, some symptoms may be subtle and difficult to assess, particularly in those with persistent AF and ablation can still be helpful in these patients. In the future, ablation may also be able to sufficiently reduce AF burden enough to reduce the risk of stroke and other morbidities. Determining if a patient is truly asymptomatic
For patients who have had AF for a long period of time, particularly persistent AF, the symptoms may initially be quite subtle such that patients are mistaken for being asymptomatic. Frequently, patients will say that they are not aware of symptoms but may overlook subtle changes such as progressive fatigue or exercise intolerance and blame this on other factors such as ‘getting older’. Despite the lack of overt symptoms, AF ablation could be a feasible way to improve the wellbeing in these patients. Mohanty et al. recently showed that ablation could improve the quality of life and exercise tolerance in patients with asymptomatic, long-standing persistent AF [25]. Interestingly, patients with AF recurrence after ablation were usually more symptomatic before ablation, perhaps indicating doi: 10.1586/14779072.2015.1011128
that the changes between sinus rhythm and AF increased AF perception. Patients with arrhythmia-associated cardiomyopathy may also not notice progressive symptoms, although left-ventricular dysfunction may have more substantial long-term prognostic implications; therefore, a more careful assessment of symptoms may be of benefit in otherwise asymptomatic AF. A trial of cardioversion may be particularly useful in assessing whether symptoms are secondary to AF or not [26]. Thus, when a patient presents with ‘asymptomatic’ AF, a careful consultation to elicit features such as progressive decline in exercise tolerance or excessive fatigue is required to ensure that subtle symptoms are not being missed. Can AF ablation reduce the risk of stroke?
If a patient’s AF is truly asymptomatic, then performing ablation would only be justified if it could reduce the risk of stroke or mortality. From a patient’s perspective, many want AF ablation in order to come off daily oral anticoagulation; however, there is no definitive proof that reduction of AF burden by ablation can eliminate the need for therapeutic anticoagulation. Expert Rev. Cardiovasc. Ther.
informahealthcare.com
[36]
65% with CHADS2 ‡1 Single center Gaita et al. (2014)
AK: Anticoagulation; pts: Patients.
Multicenter registry Bunch et al. (2011)
766
60.5
84% = 0/1; 16% ‡2; 5% ‡3
0.2% stroke (in AK stopped pts)
[35]
1.5% stroke in ablation arm Not stated 20% = 0; 20% = 1; 5% = 2; 55% >2 36
36 812 Multi-center registry Reynolds et al. (2012)
4212
[34]
3.4% stroke/TIA (in all pts) 40%
[54]
1% stroke (in AK stopped pts) 60% Mean 1.1 34 Single center Guiot et al. (2012)
1016
[33]
64% Multicenter registry Hunter et al. (2012)
1273
36
57% = 0; 34% = 1; 7% = 2 In those with stopped AK
0.16% stroke/TIA (in AK stopped pts)
[32]
82% Single center Yagishita et al. (2011)
524
44
85% = 0 – 1; 15% ‡2
0.16% stroke/TIA (in AK stopped pts)
[31]
0 91% Mean 1.89 46 Single center Saad et al. (2011)
327
[30]
1.5% stroke/TIA (in all pts) Not clear Median 1 39 Single center Chao et al. (2011)
565
[29]
80.2% Multicenter, retrospective study Themistoclakis et al. (2010)
3555
28
60% = 0; 27% = 1; 13% = 2
0.04% stroke (in AK stopped pts)
[28]
0.4% (in AK stopped pts) 84% Not stated; mean about 1 26 Single center Nademanee et al. (2008)
517
[27]
0 (in AK stopped pts) 78% with CHADS2 0; 68% ‡1 Not stated 25 Single center Oral et al. (2006)
522
Ref. Events/year % of pts with stopped AK CHADS2 score Follow-up (months) Study type
Number of pts
Special Report
Study (year)
To date, several observational studies have investigated the risk of stroke after AF ablation, mainly including patients with a lowto-intermediate risk of stroke. (TABLE 1) [27–36]. Although anticoagulation was stopped in varying proportions of patients, the risk of stroke was generally low in all of these studies and was lower than what would be expected based on the CHADS2 or CHA2DS2-VASc score. The largest study was performed by Reynolds and colleagues [34] who used a large cohort of AF ablation patients from insurance databases that were propensity matched to a control group of AF patients not receiving ablation. Over a 3-year follow-up, they reported an annual stroke risk of 1.6% for patients after AF ablation and 2.7% on antiarrhythmic drugs. Oral anticoagulation was administered in 60% of patients over the entire follow-up period. The overall stroke risk in the ablation group was lower than that predicted by their CHADS2 score, consistent with the findings of other studies reported in TABLE 1. This may suggest that ablation reduces AF burden sufficiently to reduce the risk of stroke; however, it is also possible that patients selected for ablation have confounding factors such as better vitality that make them good candidates for ablation and reduce their overall stroke risk. We also know that AF ablation is not 100% effective and episodes of asymptomatic AF can persist post-ablation [37]. Furthermore, data suggest that as little as 5.5 h [38] or even 6 min [39] of AF per month could substantially increase stroke risk. But, we must remember that all these studies and use of technologies remain hypothesis generating, and only large, prospective randomized trials will inform us on the safety of stopping therapeutic anticoagulation after AF ablation and the factors influencing the subsequent risk of stroke (e.g., AF recurrence, AF burden, underlying diseases). It is on this basis that the OCEAN trial [40] was designed to assess if ongoing oral anticoagulation would be superior to antiplatelet therapy alone in patients at intermediate risk of stroke after successful AF ablation. Until such results are available, current guidelines suggesting ongoing therapeutic anticoagulation in higher risk patients should be followed. Today, more advanced means of longterm monitoring of AF burden are available, such as implantable loop recorders (ILR).
Table 1. Studies investigating stroke risk after AF ablation.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Catheter ablation for asymptomatic atrial fibrillation?
doi: 10.1586/14779072.2015.1011128
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Special Report
¨ user & Verma Kochha
Recently, several studies showed the impact of ILRs on AF diagnosis and the clarification of AF-related diseases. ILRs can establish the diagnosis of AF in patients with cryptogenic stroke [41–43] and are superior to intermittent ECG-recording in detecting AF after ablation [37,44] or ablation of typical atrial flutter [45]. The ability to also detect asymptomatic episodes of AF is especially useful in the context of AF ablation since several studies have showed a significant increase in asymptomatic AF episodes after ablation [37,46–48]. The prospective, multicenter DISCERN-study used ILRs and patient diaries to investigate the relationship between symptomatic and asymptomatic AF episodes before and after AF ablation [37]. Results showed an increase in asymptomatic to symptomatic episodes from 1.1 before ablation to 3.7 after ablation. The reasons for this change in arrhythmia perception are difficult to assess, and since there are no blinded studies on AF ablation, a placebo effect cannot be ruled out. Besides the changes in arrhythmia perception, the DISCERN-study also showed significant changes in AF characteristics after ablation. The duration of AF episodes was significantly reduced as along with heart rate and heart rate variability during AF, which might partially be associated with changes in the autonomic nervous system. All of these changes can also contribute to the observed reduction of AF perception. The routine use of such technology postablation may help to identify those patients in whom therapeutic anticoagulation may be safely stopped because of adequate AF burden reduction.
mortality. AF ablation provides better rhythm control compared to drug therapy and does not have long-term impacts on morbidity or mortality such as with amiodarone. Since AF is a progressive disease, it is tempting to carry out AF ablation in young patients to stop AF progression. This is reflected in current guidelines by the fact that AF ablation should only be considered prior to antiarrhythmic drug treatment in younger patients without underlying disease. Principally, younger patients are more likely to benefit from the prognostic impact of AF ablation. Again, these remain hypothetical reasons why ablation may yet improve mortality in higher risk patients, but ultimately, only large-scale, randomized trials like the CABANA trial (clinicaltrials.gov, [52]) and EAST [53] will offer more insights into the impact of AF ablation on long-term morbidity and mortality.
Can AF ablation reduce the risk of mortality?
Financial & competing interests disclosure
AF is known to significantly increase mortality, mainly through an increased stroke risk and other thromboembolic events [49–51]. Yet, to date, there is no evidence that rhythm control is superior to rate control in terms of mortality; however, these trials utilized antiarrhythmic agents for rhythm control. This was an important limitation since the overall rate of sinus rhythm was not that different in the rate versus rhythm control groups due to the limited efficacy of drug therapy. Furthermore, antiarrhythmic drugs can increase the risk of both morbidity and
S Kochha¨user is supported by a research grant of the German Cardiac Society (DGK). A Verma has received research funding from and has acted on the advisory board for Boehringer Ingelheim and Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Expert commentary & five-year view
In 5 years from now, prospective studies will improve our knowledge of the influence of AF ablation on long-term outcomes and especially on the risk of stroke. ILRs could make it possible to reliably identify patients in which AF has been ‘cured’ by ablation and that have a low risk of recurrence. If AF ablation offers an improvement of morbidity in a subset of patients (e.g., young, otherwise healthy patients), it can also be a reasonable alternative for patients with asymptomatic AF, but for the majority of patients it will still be restricted to symptomatic relief.
Key issues .
Ablation of atrial fibrillation (AF) is a well-established therapy for patients with symptomatic AF and is more effective than drug treatment alone.
.
Despite recent developments in the identification of additional targets for ablation, long-term success is still not sufficient. Undetected, asymptomatic recurrences may continue and limit the potential for ablation to reduce stroke risk or mortality.
.
Smaller studies indicate that ablation may reduce the risk of stroke in AF patients, but it is unclear if this is due to AF burden reduction or confounding factors.
.
Prospective studies, such as OCEAN, investigating the effect of AF ablation on the risk of stroke are needed to evaluate the effects of AF ablation on the risk of stroke in AF patients.
.
Improvements in ablation technique and better tools for long-term AF detection may lead to a significant change in the risk–benefit ratio for AF ablation, making it a reasonable treatment for asymptomatic patients also.
doi: 10.1586/14779072.2015.1011128
Expert Rev. Cardiovasc. Ther.
Catheter ablation for asymptomatic atrial fibrillation?
a randomized trial. JAMA 2005;293(21): 2634-40
References
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1.
Wilke T, Groth A, Mueller S, et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace 2013;15(4):486-93
2.
Piccini JP, Hammill BG, Sinner MF, et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993-2007. Circ Cardiovasc Qual Outcomes 2012;5(1):85-93
3.
Wong CX, Brooks AG, Lau DH, et al. Factors associated with the epidemic of hospitalizations due to atrial fibrillation. Am J Cardiol 2012;110(10):1496-9
4.
Savelieva I, Paquette M, Dorian P, et al. Quality of life in patients with silent atrial fibrillation. Heart 2001;85(2):216-17
5.
Miyasaka Y, Barnes ME, Bailey KR, et al. Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year communitybased study. J Am Coll Cardiol 2007;49(9): 986-92
6.
Rietbrock S, Heeley E, Plumb J, et al. Chronic atrial fibrillation: incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme. Am Heart J 2008;156(1):57-64
7.
Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012;366(2):120-9
8.
Kalantarian S, Stern TA, Mansour M, et al. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann Intern Med 2013;158(5 Pt 1):338-46
9.
10.
11.
12.
Groenveld HF, Tijssen JG, Crijns HJ, et al. Rate control efficacy in permanent atrial fibrillation: successful and failed strict rate control against a background of lenient rate control: data from RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation). J Am Coll Cardiol 2013;61(7):741-8 Skanes AC, Healey JS, Cairns JA, et al. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012;28(2):125-36 Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998; 339(10):659-66 Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation:
informahealthcare.com
Special Report
for atrial fibrillation. J Am Coll Cardiol 2012;59(2):143-9
13.
Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European heart rhythm association. Eur Heart J 2012;33(21):2719-47
23.
January CT, Wann LS, Alpert JS, 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. J Am Coll Cardiol 2014;64(21):e1-76
14.
Calkins H, Reynolds MR, Spector P, et al. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol 2009;2(4):349-61
24.
15.
Parkash R, Tang AS, Sapp JL, et al. Approach to the catheter ablation technique of paroxysmal and persistent atrial fibrillation: a meta-analysis of the randomized controlled trials. J Cardiovasc Electrophysiol 2011;22(7):729-38
Forleo GB, De Martino G, Mantica M, et al. Clinical impact of catheter ablation in patients with asymptomatic atrial fibrillation: the IRON-AF (Italian registry on NavX atrial fibrillation ablation procedures) study. Int J Cardiol 2013; 168(4):3968-70
25.
Mohanty S, Santangeli P, Mohanty P, et al. Catheter ablation of asymptomatic longstanding persistent atrial fibrillation: impact on quality of life, exercise performance, arrhythmia perception, and arrhythmia-free survival. J Cardiovasc Electrophysiol 2014;25(10):1057-64
26.
Verma A, Cairns JA, Mitchell LB, et al. 2014 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation. Can J Cardiol 2014;30(10):1114-30
27.
Oral H, Chugh A, Ozaydin M, et al. Risk of thromboembolic events after percutaneous left atrial radiofrequency ablation of atrial fibrillation. Circulation 2006;114(8):759-65
28.
Nademanee K, Schwab MC, Kosar EM, et al. Clinical outcomes of catheter substrate ablation for high-risk patients with atrial fibrillation. J Am Coll Cardiol 2008;51(8): 843-9
29.
Themistoclakis S, Corrado A, Marchlinski FE, et al. The risk of thromboembolism and need for oral anticoagulation after successful atrial fibrillation ablation. J Am Coll Cardiol 2010;55(8):735-43
30.
Chao TF, Lin YJ, Tsao HM, et al. CHADS (2) and CHA(2)DS(2)-VASc scores in the prediction of clinical outcomes in patients with atrial fibrillation after catheter ablation. J Am Coll Cardiol 2011;58(23):2380-5
31.
Saad EB, d’Avila A, Costa IP, et al. Very low risk of thromboembolic events in patients undergoing successful catheter ablation of atrial fibrillation with a CHADS2 score
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Catheter ablation for asymptomatic atrial fibrillation? Expert Rev. Cardiovasc. Ther. Early online, 1–6 (2015)
Simon Kochha¨user and Atul Verma* Southlake Regional Health Centre, 602-581 Davis Dr, Newmarket, Ontario L3Y 2P6, Canada *Author for correspondence: Tel.: +1 905 953 7917 Fax: +1 905 953 0046 [email protected]
Ablation therapy for atrial fibrillation (AF) has been shown to be more efficient than medical treatment alone. Long-term success of AF ablation is still around 50% after one ablation and higher after two, with a substantial amount of asymptomatic recurrences in formerly symptomatic patients. Given the lack of evidence for superiority of rhythm control over rate control in terms of stroke reduction and mortality, AF ablation remains a treatment for symptom reduction only, although ablation has never been a part of these studies. There is early evidence that ablation could decrease the long-term risk of stroke; however, prospective studies are needed to assess whether this is the case and how patients with a successful ablation can be identified. If AF ablation can be shown to improve long-term morbidity, it could also become a reasonable treatment for patients with asymptomatic AF. KEYWORDS: ablation . anticoagulation . atrial fibrillation . outcome . stroke
Atrial fibrillation (AF) is one of the most common arrhythmic disorders with an increasing prevalence in older people [1,2]. Considering current demographic trends, the impact of AF on health care systems is expected to be increasingly burdensome [3]. AF is a progressive disease that often begins in a paroxysmal pattern and progresses to persistent AF with longer and more frequent episodes. AF significantly contributes to morbidity and mortality by causing symptoms such as fatigue, palpitations and shortness of breath in varying severity and also increasing the risk of stroke, neurodegenerative disease and even death [2,4–8]. There are two main therapy strategies in the treatment of AF. One is rate control, which aims to keep the resting heart rate at less than 100 bpm [9,10]. Rhythm control includes rate control but also attempts to restore and maintain sinus rhythm as often and for as long as possible. The first-line treatment for rhythm control is the use of antiarrhythmic drugs to suppress AF and prevent its progression. The discovery of focal activity generated from the pulmonary veins (PV) as a key trigger of AF [11] introduced electrical isolation of the PVs by catheter ablation as an interventional therapy for AF. Several studies have showed that PV isolation is an effective informahealthcare.com
10.1586/14779072.2015.1011128
tool for reducing AF burden and symptoms in formerly symptomatic patients [12–15] and is often more effective in reducing AF recurrence than antiarrhythmic drugs [12,16–18]. This is true for patients with paroxysmal and persistent AF, although success rates are significantly lower in persistent AF [14,16]. Despite its efficacy, ablation has never been shown to reduce stroke or mortality. In fact, older trials comparing rate control with rhythm control showed no benefit of the latter and perhaps a trend toward increased stroke [19,20]. Although generally more efficient at preventing AF recurrence compared to drug treatment, as an invasive treatment, ablation carries important and serious complications that remain at 1–2% [21,22]. Another advantage of drug therapy, not to be underestimated nowadays, is the lower short-term cost when compared to the fairly elaborate procedure of AF ablation. For these reasons, ablation has remained a therapy for improvement of quality of life in symptomatic patients (FIGURE 1) [13,16,23]. Following the current guideline recommendations, experience on the efficacy and safety of AF ablation in asymptomatic patients is scarce. A substudy of a prospective Italian registry showed that AF recurrence and complication rates were comparable between patients
2015 Informa UK Ltd
ISSN 1477-9072
1
Special Report
¨ user & Verma Kochha
Algorithm for rate vs rhythm control for patients with symptomatic AF Symptomatic AF
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Special circumstances in which to consider early rhythm control: • Highly symptomatic • Multiple recurrences • Extreme impairment in QOL • Arrhythmia-induced cardiomyopathy
Attempt rate control: β-blocker Calcium channel blocker
Symptoms resolve
Yes
Continue rate control
No Modify rate control consider rhythm control Paroxysmal AF High burden recurrence
Low burden recurrence Pill in pocket anti-arrhythmic therapy
Persistent AF
Maintenance anti-arrhythmic therapy
Consider cardioversion
Symptoms improve, but AF recurs
Catheter ablation
Symptoms improve, and patient maintains sinus rhythm
Symptoms do not change in sinus rhythm and AF recurs
Observe, if AF recurs, determine if symptomatic
Figure 1. Decision algorithm for rate or rhythm control in patients with symptomatic atrial fibrillation. Reprinted from the “2014 focused update of the Canadian Cardiovascular Society guidelines for the management of atrial fibrillation” [26] with permission from Elsevier.
with and without symptoms [24]; however, some symptoms may be subtle and difficult to assess, particularly in those with persistent AF and ablation can still be helpful in these patients. In the future, ablation may also be able to sufficiently reduce AF burden enough to reduce the risk of stroke and other morbidities. Determining if a patient is truly asymptomatic
For patients who have had AF for a long period of time, particularly persistent AF, the symptoms may initially be quite subtle such that patients are mistaken for being asymptomatic. Frequently, patients will say that they are not aware of symptoms but may overlook subtle changes such as progressive fatigue or exercise intolerance and blame this on other factors such as ‘getting older’. Despite the lack of overt symptoms, AF ablation could be a feasible way to improve the wellbeing in these patients. Mohanty et al. recently showed that ablation could improve the quality of life and exercise tolerance in patients with asymptomatic, long-standing persistent AF [25]. Interestingly, patients with AF recurrence after ablation were usually more symptomatic before ablation, perhaps indicating doi: 10.1586/14779072.2015.1011128
that the changes between sinus rhythm and AF increased AF perception. Patients with arrhythmia-associated cardiomyopathy may also not notice progressive symptoms, although left-ventricular dysfunction may have more substantial long-term prognostic implications; therefore, a more careful assessment of symptoms may be of benefit in otherwise asymptomatic AF. A trial of cardioversion may be particularly useful in assessing whether symptoms are secondary to AF or not [26]. Thus, when a patient presents with ‘asymptomatic’ AF, a careful consultation to elicit features such as progressive decline in exercise tolerance or excessive fatigue is required to ensure that subtle symptoms are not being missed. Can AF ablation reduce the risk of stroke?
If a patient’s AF is truly asymptomatic, then performing ablation would only be justified if it could reduce the risk of stroke or mortality. From a patient’s perspective, many want AF ablation in order to come off daily oral anticoagulation; however, there is no definitive proof that reduction of AF burden by ablation can eliminate the need for therapeutic anticoagulation. Expert Rev. Cardiovasc. Ther.
informahealthcare.com
[36]
65% with CHADS2 ‡1 Single center Gaita et al. (2014)
AK: Anticoagulation; pts: Patients.
Multicenter registry Bunch et al. (2011)
766
60.5
84% = 0/1; 16% ‡2; 5% ‡3
0.2% stroke (in AK stopped pts)
[35]
1.5% stroke in ablation arm Not stated 20% = 0; 20% = 1; 5% = 2; 55% >2 36
36 812 Multi-center registry Reynolds et al. (2012)
4212
[34]
3.4% stroke/TIA (in all pts) 40%
[54]
1% stroke (in AK stopped pts) 60% Mean 1.1 34 Single center Guiot et al. (2012)
1016
[33]
64% Multicenter registry Hunter et al. (2012)
1273
36
57% = 0; 34% = 1; 7% = 2 In those with stopped AK
0.16% stroke/TIA (in AK stopped pts)
[32]
82% Single center Yagishita et al. (2011)
524
44
85% = 0 – 1; 15% ‡2
0.16% stroke/TIA (in AK stopped pts)
[31]
0 91% Mean 1.89 46 Single center Saad et al. (2011)
327
[30]
1.5% stroke/TIA (in all pts) Not clear Median 1 39 Single center Chao et al. (2011)
565
[29]
80.2% Multicenter, retrospective study Themistoclakis et al. (2010)
3555
28
60% = 0; 27% = 1; 13% = 2
0.04% stroke (in AK stopped pts)
[28]
0.4% (in AK stopped pts) 84% Not stated; mean about 1 26 Single center Nademanee et al. (2008)
517
[27]
0 (in AK stopped pts) 78% with CHADS2 0; 68% ‡1 Not stated 25 Single center Oral et al. (2006)
522
Ref. Events/year % of pts with stopped AK CHADS2 score Follow-up (months) Study type
Number of pts
Special Report
Study (year)
To date, several observational studies have investigated the risk of stroke after AF ablation, mainly including patients with a lowto-intermediate risk of stroke. (TABLE 1) [27–36]. Although anticoagulation was stopped in varying proportions of patients, the risk of stroke was generally low in all of these studies and was lower than what would be expected based on the CHADS2 or CHA2DS2-VASc score. The largest study was performed by Reynolds and colleagues [34] who used a large cohort of AF ablation patients from insurance databases that were propensity matched to a control group of AF patients not receiving ablation. Over a 3-year follow-up, they reported an annual stroke risk of 1.6% for patients after AF ablation and 2.7% on antiarrhythmic drugs. Oral anticoagulation was administered in 60% of patients over the entire follow-up period. The overall stroke risk in the ablation group was lower than that predicted by their CHADS2 score, consistent with the findings of other studies reported in TABLE 1. This may suggest that ablation reduces AF burden sufficiently to reduce the risk of stroke; however, it is also possible that patients selected for ablation have confounding factors such as better vitality that make them good candidates for ablation and reduce their overall stroke risk. We also know that AF ablation is not 100% effective and episodes of asymptomatic AF can persist post-ablation [37]. Furthermore, data suggest that as little as 5.5 h [38] or even 6 min [39] of AF per month could substantially increase stroke risk. But, we must remember that all these studies and use of technologies remain hypothesis generating, and only large, prospective randomized trials will inform us on the safety of stopping therapeutic anticoagulation after AF ablation and the factors influencing the subsequent risk of stroke (e.g., AF recurrence, AF burden, underlying diseases). It is on this basis that the OCEAN trial [40] was designed to assess if ongoing oral anticoagulation would be superior to antiplatelet therapy alone in patients at intermediate risk of stroke after successful AF ablation. Until such results are available, current guidelines suggesting ongoing therapeutic anticoagulation in higher risk patients should be followed. Today, more advanced means of longterm monitoring of AF burden are available, such as implantable loop recorders (ILR).
Table 1. Studies investigating stroke risk after AF ablation.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Catheter ablation for asymptomatic atrial fibrillation?
doi: 10.1586/14779072.2015.1011128
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Nyu Medical Center on 02/12/15 For personal use only.
Special Report
¨ user & Verma Kochha
Recently, several studies showed the impact of ILRs on AF diagnosis and the clarification of AF-related diseases. ILRs can establish the diagnosis of AF in patients with cryptogenic stroke [41–43] and are superior to intermittent ECG-recording in detecting AF after ablation [37,44] or ablation of typical atrial flutter [45]. The ability to also detect asymptomatic episodes of AF is especially useful in the context of AF ablation since several studies have showed a significant increase in asymptomatic AF episodes after ablation [37,46–48]. The prospective, multicenter DISCERN-study used ILRs and patient diaries to investigate the relationship between symptomatic and asymptomatic AF episodes before and after AF ablation [37]. Results showed an increase in asymptomatic to symptomatic episodes from 1.1 before ablation to 3.7 after ablation. The reasons for this change in arrhythmia perception are difficult to assess, and since there are no blinded studies on AF ablation, a placebo effect cannot be ruled out. Besides the changes in arrhythmia perception, the DISCERN-study also showed significant changes in AF characteristics after ablation. The duration of AF episodes was significantly reduced as along with heart rate and heart rate variability during AF, which might partially be associated with changes in the autonomic nervous system. All of these changes can also contribute to the observed reduction of AF perception. The routine use of such technology postablation may help to identify those patients in whom therapeutic anticoagulation may be safely stopped because of adequate AF burden reduction.
mortality. AF ablation provides better rhythm control compared to drug therapy and does not have long-term impacts on morbidity or mortality such as with amiodarone. Since AF is a progressive disease, it is tempting to carry out AF ablation in young patients to stop AF progression. This is reflected in current guidelines by the fact that AF ablation should only be considered prior to antiarrhythmic drug treatment in younger patients without underlying disease. Principally, younger patients are more likely to benefit from the prognostic impact of AF ablation. Again, these remain hypothetical reasons why ablation may yet improve mortality in higher risk patients, but ultimately, only large-scale, randomized trials like the CABANA trial (clinicaltrials.gov, [52]) and EAST [53] will offer more insights into the impact of AF ablation on long-term morbidity and mortality.
Can AF ablation reduce the risk of mortality?
Financial & competing interests disclosure
AF is known to significantly increase mortality, mainly through an increased stroke risk and other thromboembolic events [49–51]. Yet, to date, there is no evidence that rhythm control is superior to rate control in terms of mortality; however, these trials utilized antiarrhythmic agents for rhythm control. This was an important limitation since the overall rate of sinus rhythm was not that different in the rate versus rhythm control groups due to the limited efficacy of drug therapy. Furthermore, antiarrhythmic drugs can increase the risk of both morbidity and
S Kochha¨user is supported by a research grant of the German Cardiac Society (DGK). A Verma has received research funding from and has acted on the advisory board for Boehringer Ingelheim and Bayer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Expert commentary & five-year view
In 5 years from now, prospective studies will improve our knowledge of the influence of AF ablation on long-term outcomes and especially on the risk of stroke. ILRs could make it possible to reliably identify patients in which AF has been ‘cured’ by ablation and that have a low risk of recurrence. If AF ablation offers an improvement of morbidity in a subset of patients (e.g., young, otherwise healthy patients), it can also be a reasonable alternative for patients with asymptomatic AF, but for the majority of patients it will still be restricted to symptomatic relief.
Key issues .
Ablation of atrial fibrillation (AF) is a well-established therapy for patients with symptomatic AF and is more effective than drug treatment alone.
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Despite recent developments in the identification of additional targets for ablation, long-term success is still not sufficient. Undetected, asymptomatic recurrences may continue and limit the potential for ablation to reduce stroke risk or mortality.
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Smaller studies indicate that ablation may reduce the risk of stroke in AF patients, but it is unclear if this is due to AF burden reduction or confounding factors.
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Prospective studies, such as OCEAN, investigating the effect of AF ablation on the risk of stroke are needed to evaluate the effects of AF ablation on the risk of stroke in AF patients.
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Improvements in ablation technique and better tools for long-term AF detection may lead to a significant change in the risk–benefit ratio for AF ablation, making it a reasonable treatment for asymptomatic patients also.
doi: 10.1586/14779072.2015.1011128
Expert Rev. Cardiovasc. Ther.
Catheter ablation for asymptomatic atrial fibrillation?
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