==Pharmacological treatment of atrial fibrillation==
The main goals of treatment of atrial fibrillation are to prevent temporary circulatory instability and to prevent [[stroke]]. Rate and rhythm control are principally used to achieve the former, while [[anticoagulation]] may be required to decrease the risk of the latter.<ref>{{cite journal | author=Prystowsky EN | title=Management of atrial fibrillation: therapeutic options and clinical decisions | journal=Am J Cardiol | year=2000 | pages=3D-11D | volume=85 | issue=10A }} PMID 10822035</ref> In emergencies, when circulatory collapse is imminent due to uncontrolled [[tachycardia]], immediate [[cardioversion]] may be indicated.<ref name="pmid16908781"/>
The primary factors determining atrial fibrillation treatment are duration and evidence of hemodynamic instability. [[Cardioversion]] is indicated with new onset AF (for less than 48 hours) and with hemodynamic instability. If rate and rhythm control cannot be maintained by medication or cardioversion, [[Cardiac electrophysiology|electrophysiological studies]] with pathway [[Radiofrequency ablation|ablation]] may be required.<ref name="pmid16908781"/>
=== Antithrombotic Strategies for Prevention of Ischemic Stroke and Systemic Embolism ===
Oral anticoagulation is a mainstay of atrial fibrillation management. For both primary and secondary prevention of stroke, there is a 61% relative risks reduction in the incidence of all cause stroke (both ischemic and hemorrhagic) associated with adjusted-dose oral anticoagulation.<ref name="pmid">{{cite journal |author=Hart RG, Benavente O, McBride R, Pearce LA |title=Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis |journal=Ann. Intern. Med. |volume=131 |issue=7 |pages=492–501 |year=1999 |month=October |pmid= |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=10507957}}</ref>
Increasing patient age (which is associated with smaller body weight, female gender and a progressive decline in renal function) and higher INRs or greater intensity of anticoagulation are both associated with a higher risk of major bleeding. This is critical in so far as bleeding is in turn associated with non-compliance with pharmacotherapy. <ref name="pmid">{{cite journal |author= |title=Bleeding during antithrombotic therapy in patients with atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators |journal=Arch. Intern. Med. |volume=156 |issue=4 |pages=409–16 |year=1996 |month=February |pmid= |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=8607726}}</ref><ref name="pmid10522891">{{cite journal |author=Gorter JW |title=Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups |journal=Neurology |volume=53 |issue=6 |pages=1319–27 |year=1999 |month=October |pmid=10522891 |doi= |url=http://www.neurology.org/cgi/pmidlookup?view=long&pmid=10522891}}</ref><ref name="pmid8172435">{{cite journal |author=Hylek EM, Singer DE |title=Risk factors for intracranial hemorrhage in outpatients taking warfarin |journal=Ann. Intern. Med. |volume=120 |issue=11 |pages=897–902 |year=1994 |month=June |pmid=8172435 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=8172435}}</ref> <ref name="pmid">{{cite journal |author=Fihn SD, Callahan CM, Martin DC, McDonell MB, Henikoff JG, White RH |title=The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics |journal=Ann. Intern. Med. |volume=124 |issue=11 |pages=970–9 |year=1996 |month=June |pmid= |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=8624064}}</ref><ref name="pmid10577332">{{cite journal |author=Hart RG, Halperin JL |title=Atrial fibrillation and thromboembolism: a decade of progress in stroke prevention |journal=Ann. Intern. Med. |volume=131 |issue=9 |pages=688–95 |year=1999 |month=November |pmid=10577332 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=10577332}}</ref> Given that many patients with atrial fibrillation are elderly, there is often a narrow therapeutic window in achieving the optimal INR. The optimal INR should obviously maximize efficacy in reducing the risk of stroke and simultaneously minimize the risk of bleeding. In the setting of atrial fibrillation, an INR of 2 to 3 appears to be optimal. INRs lower than this, such as those in the range of 1.6 to 2.5, are associated with efficacy that is only 80% of that in the target range.<ref name="pmid8678931">{{cite journal |author=Hylek EM, Skates SJ, Sheehan MA, Singer DE |title=An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation |journal=N. Engl. J. Med. |volume=335 |issue=8 |pages=540–6 |year=1996 |month=August |pmid=8678931 |doi= |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=8678931&promo=ONFLNS19}}</ref><ref name="pmid8782752">{{cite journal |author= |title=Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial |journal=Lancet |volume=348 |issue=9028 |pages=633–8 |year=1996 |month=September |pmid=8782752 |doi= |url=}}</ref> <ref name="pmid7776995">{{cite journal |author= |title=Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. The European Atrial Fibrillation Trial Study Group |journal=N. Engl. J. Med. |volume=333 |issue=1 |pages=5–10 |year=1995 |month=July |pmid=7776995 |doi= |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=7776995&promo=ONFLNS19}}</ref><ref name="pmid9490603">{{cite journal |author=Hart RG |title=Intensity of anticoagulation to prevent stroke in patients with atrial fibrillation |journal=Ann. Intern. Med. |volume=128 |issue=5 |pages=408 |year=1998 |month=March |pmid=9490603 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=9490603}}</ref>
====Interruption of anticoagulation with coumadin====
No mechanical valve, high risk of bleeding with procedure: Coumadin can be discontinued for one week without heparin bridging.
Presence of mechanical valve, patients with AF who are at high risk of stroke, or patients in whom Coumadin must be interrupted for over a week: These patients should be administered either [[unfractionated heparin]] or [[low molecular weight heparin]].
====Investigational antithrombin agents====
Newer agents that inhibit [[factor Xa]] are under investigation for the management of atrial fibrillation. These agents include [[apixabin]] and [[rivaroxaban]].
====Antiplatelet therapy for atrial fibrillation====
=====Aspirin Monotherapy=====
Aspirin monotherapy is associated with only a modest and inconsistent reduction in the risk of stroke associated with atrial fibrillation. <ref name="pmid9490603">{{cite journal |author=Hart RG |title=Intensity of anticoagulation to prevent stroke in patients with atrial fibrillation |journal=Ann. Intern. Med. |volume=128 |issue=5 |pages=408 |year=1998 |month=March |pmid=9490603 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=9490603}}</ref> <ref name="pmid9490603">{{cite journal |author=Hart RG |title=Intensity of anticoagulation to prevent stroke in patients with atrial fibrillation |journal=Ann. Intern. Med. |volume=128 |issue=5 |pages=408 |year=1998 |month=March |pmid=9490603 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=9490603}}</ref>
<ref name="pmid9183235">{{cite journal |author= |title=The efficacy of aspirin in patients with atrial fibrillation. Analysis of pooled data from 3 randomized trials. The Atrial Fibrillation Investigators |journal=Arch. Intern. Med. |volume=157 |issue=11 |pages=1237–40 |year=1997 |month=June |pmid=9183235 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=9183235}}</ref> Studies suggest that the efficacy of aspirin may be greater in patients with [[hypertension]] or [[ diabetes]]. Aspirin may also be more efficacious in reducing the risk of non cardioembolic stroke as opposed to the more disabling cardioembolic form of stroke. <ref name="pmid8423907">{{cite journal |author=Miller VT, Rothrock JF, Pearce LA, Feinberg WM, Hart RG, Anderson DC |title=Ischemic stroke in patients with atrial fibrillation: effect of aspirin according to stroke mechanism. Stroke Prevention in Atrial Fibrillation Investigators |journal=Neurology |volume=43 |issue=1 |pages=32–6 |year=1993 |month=January |pmid=8423907 |doi= |url=}}</ref><ref name="pmid10629345">{{cite journal |author=Hart RG, Pearce LA, Miller VT, ''et al'' |title=Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies |journal=Cerebrovasc. Dis. |volume=10 |issue=1 |pages=39–43 |year=2000 |pmid=10629345 |doi= |url=http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=ced10039}}</ref>
=====Dual Antiplatelet therapy=====
Among patients who are not deemed candidates for [[Coumadin]] therapy (estimated to be approximately 40-50% of patients), dual antiplatelet therapy with both [[aspirin]] and [[clopidogrel]] (at a maintenance dose of 75 mg/day) was superior to [[aspirin]] monotherapy in the [[ACTIVE A trial]]. The primary endpoint of the trial was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes. After a median of 3.6 years of follow-up in 7,554 randomized patients, the addition of [[clopidogrel]] to [[aspirin]] alone yielded a reduction in events from 7.6% to 6.8% (relative risk reduction with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The addition of [[clopidogrel]] to [[aspirin]] alone reduced the risk of stroke by 28% (from 3.3% to 2.4%, p<0.001) and reduced the risk of MI by 22% (from 0.9% per year to 0.7% per year, p=0.08). The risk of major bleeding among patients treated with aspirin and clopidogrel was 2.0% per year whereas it was 1.3% per year among patients treated with aspirin alone (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001). If 1000 patients were treated for 3 years, the combination of aspirin plus clopidogrel would prevent 28 strokes (17 disabling or fatal), and 6 myocardial infarctions, at a cost of 20 major bleeds compared to aspirin alone.
====Oral Anticoagulation (Coumadin) versus Dual Antiplatelet Therapy (ASA/Clopidogrel)====
In the ACTIVE W trial, dual antiplatelet therapy with [[aspirin]](75-100 mg per day) and [[clopidogrel]] (75 mg per day) was found to be statistically inferior to [[coumadin]] therapy (target INR 2.0 to 3.0) in the management of patients with [[atrial fibrillation]] who had one or more risk factors for [[stroke]]<ref> The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>. The primary endpoint of ACTIVE W was the first occurrence of [[stroke]], non-CNS systemic embolus, [[myocardial infarction]], or vascular death. The annual risk in the [[coumadin]] group was 3.93% per year, and in the [[Aspirin]]/[[Clopidogrel]] group it was 5.60% per year yielding a relative risk of 1.44 (1.18-1.76; p=0.0003). The efficacy was not as great among patients who were coumadin naive, although the p-value for the interaction was negative. There was no excess bleeding among patients treated with [[coumadin]], and in fact there was an excess of minor bleeds among patients treated with [[ASA]] and [[clopidogrel]] (13.6% / yr vs 11.5% year, p=0.0009).
When examining the data from atrial fibrillation trials, it is critical to evaluate the results in patients who were previously treated with [[coumadin]] separate from those patients who were naive to coumadin. Patients previously treated with coumadin are likely to be those patients who best tolerate coumadin and have passed their "bleeding stress test" and have a lower rate of bleeding on coumadin. Those patients who bleed while on [[coumadin]] have already been culled out from the population. When the data in ACTIVE W were evaluated including only those patients previously treated with [[coumadin]](again a population to be anticipated to be at low risk of bleeding), the risk of major bleeding was indeed statistically significantly lower among patients previously treated with coumadin (p=0.03) than patients not previously treated.
The majority of the reduction in events was due to a reduction in [[stroke]] and non-CNS emolization associated with [[coumadin therapy. The pathophysiology of stroke among patients with atrial fibrillation is thought to be embolization from clot in the [[left atrium]]. The data from ACTIVE W suggest that platelet activation and its treatment may not play a pivotal role in the treatment of mural thrombus and embolization in atrial fibrillation. Coumadin was more effective in the reduction of non-disabling stroke rather than disabling stroke. There were more fatal hemorrhagic strokes (which may more often be fatal), and this may explain in part why coumadin was not associated with a reduction in mortality in the study.
While clopidogrel plus aspirin has been found to reduce the risk of recurrent [[myocardial infarction]] among patients with presumed plaque rupture and [[acute coronary syndromes]], it is notable in ACTIVE W that the risk of [[myocardial infarction]] tended to be higher among patients treated with [[aspirin]] plus [[clopidogrel]] versus [[coumadin]] (0.86% vs 0.55%,p=0.09)<ref> The ACTIVE Writing Group on behalf of the ACTIVE Investigators. Lancet 2006;367:1903-12.</ref>.
=== Conversion to sinus rhythm and thromboembolism ===
===Electrical & mechanical dissociation===
Despite the restoration of sinus rhythm on the ECG following cardioversion (either spontaneous, pharmacologic or electrical or after radiofrequency catheter ablation of [[atrial flutter]]), in some patients there is a persistent lack of atrial contractility. This state is known as electrical mechanical dissociation and may be sue to mechanical stunning in the atrium and the atrial appendage. <ref name="pmid8294679">{{cite journal |author=Fatkin D, Kuchar DL, Thorburn CW, Feneley MP |title=Transesophageal echocardiography before and during direct current cardioversion of atrial fibrillation: evidence for "atrial stunning" as a mechanism of thromboembolic complications |journal=J. Am. Coll. Cardiol. |volume=23 |issue=2 |pages=307–16 |year=1994 |month=February |pmid=8294679 |doi= |url=}}</ref> <ref name="pmid10569673">{{cite journal |author=Antonielli E, Pizzuti A, Bassignana A, ''et al'' |title=Transesophageal echocardiographic evidence of more pronounced left atrial stunning after chemical (propafenone) rather than electrical attempts at cardioversion from atrial fibrillation |journal=Am. J. Cardiol. |volume=84 |issue=9 |pages=1092–6, A9–10 |year=1999 |month=November |pmid=10569673 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914999005081}}</ref><ref name="pmid8752189">{{cite journal |author=Falcone RA, Morady F, Armstrong WF |title=Transesophageal echocardiographic evaluation of left atrial appendage function and spontaneous contrast formation after chemical or electrical cardioversion of atrial fibrillation |journal=Am. J. Cardiol. |volume=78 |issue=4 |pages=435–9 |year=1996 |month=August |pmid=8752189 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(96)00333-5}}</ref><ref name="pmid8752189">{{cite journal |author=Falcone RA, Morady F, Armstrong WF |title=Transesophageal echocardiographic evaluation of left atrial appendage function and spontaneous contrast formation after chemical or electrical cardioversion of atrial fibrillation |journal=Am. J. Cardiol. |volume=78 |issue=4 |pages=435–9 |year=1996 |month=August |pmid=8752189 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(96)00333-5}}</ref><ref name="pmid9604945">{{cite journal |author=Bellotti P, Spirito P, Lupi G, Vecchio C |title=Left atrial appendage function assessed by transesophageal echocardiography before and on the day after elective cardioversion for nonvalvular atrial fibrillation |journal=Am. J. Cardiol. |volume=81 |issue=10 |pages=1199–202 |year=1998 |month=May |pmid=9604945 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(98)00089-7}}</ref><ref name="pmid9605054">{{cite journal |author=Harjai K, Mobarek S, Abi-Samra F, ''et al'' |title=Mechanical dysfunction of the left atrium and the left atrial appendage following cardioversion of atrial fibrillation and its relation to total electrical energy used for cardioversion |journal=Am. J. Cardiol. |volume=81 |issue=9 |pages=1125–9 |year=1998 |month=May |pmid=9605054 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914998001416}}</ref><ref name="pmid9708477">{{cite journal |author=Sparks PB, Jayaprakash S, Vohra JK, ''et al'' |title=Left atrial "stunning" following radiofrequency catheter ablation of chronic atrial flutter |journal=J. Am. Coll. Cardiol. |volume=32 |issue=2 |pages=468–75 |year=1998 |month=August |pmid=9708477 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(98)00253-8}}</ref> The lack of atrial contraction can be diagnosed on echocardiography by the appearance of spontaneous echo contrast. <ref name="pmid8294679">{{cite journal |author=Fatkin D, Kuchar DL, Thorburn CW, Feneley MP |title=Transesophageal echocardiography before and during direct current cardioversion of atrial fibrillation: evidence for "atrial stunning" as a mechanism of thromboembolic complications |journal=J. Am. Coll. Cardiol. |volume=23 |issue=2 |pages=307–16 |year=1994 |month=February |pmid=8294679 |doi= |url=}}</ref> In general, the longer the patient was in atrial fibrillation, the longer the time it takes for the recoery of atrial mechanical function. The period of recovery can be quite variable, and it can take several weeks in total. Recovery of mechanical function can be delayed for several weeks, depending in part on the duration of [[AF]] before restoration of [[sinus rhythm]]<ref name="pmid7733009">{{cite journal |author=Mitusch R, Garbe M, Schmücker G, Schwabe K, Stierle U, Sheikhzadeh A |title=Relation of left atrial appendage function to the duration and reversibility of nonvalvular atrial fibrillation |journal=Am. J. Cardiol. |volume=75 |issue=14 |pages=944–7 |year=1995 |month=May |pmid=7733009 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S000291499980695X}}</ref><ref name="pmid7887393">{{cite journal |author=Manning WJ, Silverman DI, Katz SE, ''et al'' |title=Temporal dependence of the return of atrial mechanical function on the mode of cardioversion of atrial fibrillation to sinus rhythm |journal=Am. J. Cardiol. |volume=75 |issue=8 |pages=624–6 |year=1995 |month=March |pmid=7887393 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914999806328}}</ref><ref name="pmid7611109">{{cite journal |author=Grimm RA, Leung DY, Black IW, Stewart WJ, Thomas JD, Klein AL |title=Left atrial appendage "stunning" after spontaneous conversion of atrial fibrillation demonstrated by transesophageal Doppler echocardiography |journal=Am. Heart J. |volume=130 |issue=1 |pages=174–6 |year=1995 |month=July |pmid=7611109 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0002-8703(95)90253-8}}</ref> This kind of electrical mechanical dissociation may explain in part the observation that some patients develop thromboembolic events following cardioversion despite the fact that they had no visible [[left atrial]] clot on [[TEE]]. <ref name="pmid8205657">{{cite journal |author=Black IW, Fatkin D, Sagar KB, ''et al'' |title=Exclusion of atrial thrombus by transesophageal echocardiography does not preclude embolism after cardioversion of atrial fibrillation. A multicenter study |journal=Circulation |volume=89 |issue=6 |pages=2509–13 |year=1994 |month=June |pmid=8205657 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=8205657}}</ref> It has been hypothesized that the low shear state and turbulent nature of left atrial hemodynamics during this period leads to the development of clot which then embolizes once there is restoration of sufficient mechanical force.<ref name="pmid9874066">{{cite journal |author=Berger M, Schweitzer P |title=Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis |journal=Am. J. Cardiol. |volume=82 |issue=12 |pages=1545–7, A8 |year=1998 |month=December |pmid=9874066 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S000291499800705X}}</ref> It is in part due to the presence of atrial mechanical dissociation and the risk of clot formation and embolization that oral anticoagulation is recommended for 3 to 4 weeks following successful electrical cardioversion in patients in whom the duration of Afib is unknown or in whom the duration of atrial fibrillation has been documented to be longer than 48 hours. Among patients in whom the duration of atrial fibrillation is less than 48 hours, the necessity for anticoagulation is not as clear, although it should be noted that stroke has been observed in these patients as well. No matter what the duration of atrial fibrillation, if a patient becomes hemodynamically unstable, this is an indication for immediate cardioversion.
== Management Strategies ==
=== New diagnosed or First Episode of Atrial Fibrillation ===
In patients who have self-limited episodes of paroxysmal AF, antiarrhythmic drugs to prevent recurrence are usually unnecessary, unless AF is associated with severe symptoms related to hypotension, myocardial ischemia, or HF. Whether these individuals require longterm or even short-term anticoagulation is not clear, and the decision must be individualized for each patient based on the intrinsic risk of thromboembolism.
=== Persistent Atrial Fibrillation ===
=== Recurrent Paroxysmal Atrial Fibrillation===
=== Vagally mediated [[Atrial fibrillation]]===
[[Disopyramide]] or [[flecainide]]
=== Adrenergically induced Atrial Fibrillation===
Beta blockers (sotalol)
=== Congestive Heart Failure ===
amiodarone or dofetilide to maintain sinus rhythm.
=== Ischemic heart disease ===
=== Hypertension without LVH ===
===Left ventricular hypertrophy===
==ACC / AHA Guidelines- Recommendation for Pacing to Prevent Atrial Fibrillation (DO NOT EDIT) <ref name="Epstein"> Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008; 117: 2820–2840. PMID 18483207 </ref>==
{{cquote|
===Class III===
1. Permanent [[pacemaker|pacing]] is not indicated for the prevention of AF in patients without any other indication for [[pacemaker]] implantation. ''(Level of Evidence: B)''}}
==Sources==
* The ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities <ref name="Epstein"> Epstein AE, DiMarco JP, Ellenbogen KA, Estes NAM III, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices). Circulation. 2008; 117: 2820–2840. PMID 18483207 </ref>
== Recurrent Persistent AF ==
== Permanent AF ==
===Anticoagulation===
Patients with atrial fibrillation, even lone atrial fibrillation without other evidence of heart disease, are at increased risk of stroke during long term follow up.<ref name="pmid4068186">{{cite journal |author=Brand FN, Abbott RD, Kannel WB, Wolf PA |title=Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study |journal=JAMA |volume=254 |issue=24 |pages=3449-53 |year=1985 |pmid=4068186 |doi=}}</ref> A [[systematic review]] of risk factors for [[stroke]] in patients with nonvalvular atrial fibrillation concluded that a prior history of stroke or TIA is the most powerful risk factor for future stroke, followed by advancing age, hypertension, diabetes.<ref name="pmid17679673">{{cite journal |author= |title=Independent predictors of stroke in patients with atrial fibrillation: a systematic review |journal=Neurology |volume=69 |issue=6 |pages=546-54 |year=2007 |pmid=17679673 |doi=10.1212/01.wnl.0000267275.68538.8d}}</ref> The risk of stroke increases whether the lone atrial fibrillation was an isolated episode, recurrent, or chronic.<ref name="pmid3627174">{{cite journal |author=Kopecky SL, Gersh BJ, McGoon MD, ''et al'' |title=The natural history of lone atrial fibrillation. A population-based study over three decades |journal=N. Engl. J. Med. |volume=317 |issue=11 |pages=669-74 |year=1987 |pmid=3627174 |doi=}}</ref> The risk of systemic embolization (atrial clots migrating to other organs) depends strongly on whether there is an underlying structural problem with the heart (e.g. [[mitral stenosis]]) and on the presence of other risk factors, such as diabetes and high blood pressure. Finally, patients under 65 are much less likely to develop embolization compared with patients over 75. In young patients with few risk factors and no structural heart defect, the benefits of anticoagulation may be outweighed by the risks of [[hemorrhage]] (bleeding). Those at a low risk may benefit from mild (and low-risk) anticoagulation with [[aspirin]] (or [[clopidogrel]] in those who are allergic to aspirin). In contrast, those with a high risk of stroke derive most benefit from [[anticoagulant]] treatment with [[warfarin]] or similar drugs.
In the United Kingdom, the [[National Institute for Health and Clinical Excellence|NICE]] guidelines recommend using a [[clinical prediction rule]] for this purpose.<ref name="nice">{{cite web |author=National Institute for Health and Clinical Excellence|url=http://guidance.nice.org.uk/CG36 |title=Clinical Guideline 36 - Atrial fibrillation | date=June 2006 | accessdate=2007-08-15 |format= |work=}}</ref> The ''[[CHADS Score|CHADS/CHADS2]]'' score is the best validated clinical prediction rule for determining risk of stroke (and therefore who should be anticoagulated); it assigns points (totaling 0-6) depending on the presence or absence of co-morbidities such hypertension and diabetes. In a comparison of seven [[clinical prediction rule|prediction rule]]s, the best rules were the [[CHADS Score|CHADS2]] which performed similarly to the SPAF<ref name="pmid10356104">{{cite journal |author=Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW |title=Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators |journal=Stroke |volume=30 |issue=6 |pages=1223–9 |year=1999 |pmid=10356104 |doi=}}</ref> and [[Framingham Heart Study|Framingham]]<ref name="pmid12941677">{{cite journal |author=Wang TJ, Massaro JM, Levy D, ''et al'' |title=A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study |journal=JAMA |volume=290 |issue=8 |pages=1049–56 |year=2003 |pmid=12941677 |doi=10.1001/jama.290.8.1049}}</ref> [[clinical prediction rule|prediction rule]]s. <ref name="pmid17673721">{{cite journal |author=Baruch L, Gage BF, Horrow J, ''et al'' |title=Can patients at elevated risk of stroke treated with anticoagulants be further risk stratified? |journal=Stroke |volume=38 |issue=9 |pages=2459–63 |year=2007 |pmid=17673721 |doi=10.1161/STROKEAHA.106.477133}}</ref>
To compensate for the increased risk of stroke, anticoagulants may be required. However, in the case of warfarin, if a patient has a yearly risk of stroke that is less than 2%, then the risks associated with taking warfarin outweigh the risk of getting a stroke. <ref>{{cite journal | author=van Walraven C, Hart RG, Singer DE, ''et al.'' | title=Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis | journal=JAMA | year=2002 | volume=288 | issue=19 | pages=2441–48 | url=http://jama.ama-assn.org/cgi/content/abstract/288/19/2441|id=PMID 12435257}}</ref><ref>{{cite journal | author=Gage BF, Cardinalli AB, Owens D. | title=Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation | journal=Stroke | year=1998 | volume=29 | pages=1083–91 | url=http://stroke.ahajournals.org/cgi/content/abstract/29/6/1083|id=PMID 9626276 }}</ref>
====Acute anticoagulation====
If anticoagulation is required urgently (e.g. for cardioversion), [[heparin]] or similar drugs achieve the required level of protection much quicker than warfarin, which may take several days to reach adequate levels.
In the initial stages after an embolic stroke, anticoagulation may be risky, as the damaged area of the brain is relatively prone to bleeding (hemorrhagic transformation).<ref name="pmid17204681">{{cite journal |author=Paciaroni M, Agnelli G, Micheli S, Caso V |title=Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials |journal=Stroke |volume=38 |issue=2 |pages=423-30 | year=2007 |pmid=17204681 |doi=10.1161/01.STR.0000254600.92975.1f }} [http://www.acpjc.org/Content/147/1/issue/ACPJC-2007-147-1-017.htm ACP JC synopsis ]</ref> As a result, a [[clinical practice guideline]] by [[National Institute for Health and Clinical Excellence]] recommends that anticoagulation should begin two weeks after stroke if no hemorrhage occurred.<ref name=nice/>
====Chronic anticoagulation====
Among patients with "non-valvular" atrial fibrillation, anticoagulation with warfarin can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. <ref name="pmid17577005">{{cite journal |author=Hart RG, Pearce LA, Aguilar MI |title=Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation |journal=Ann Intern Med |volume=146 |issue=12 |pages=857–67 |year=2007 |pmid=17577005 |doi=}}</ref><ref name="pmid17636831">{{cite journal |author=Aguilar M, Hart R, Pearce L |title=Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks |journal= Cochrane Database Syst Rev |volume=3 |issue= |pages=CD006186 |year=2007 |pmid=17636831 |doi=10.1002/14651858.CD006186.pub2}}</ref>. There is evidence that [[aspirin]] and [[clopidogrel]] are effective when used together, but the combination is still inferior to [[warfarin]].<ref name="pmid16765759">{{cite journal |author=Connolly S, Pogue J, Hart R, ''et al'' |title=Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial |journal=Lancet |volume=367 |issue=9526 |pages=1903–12 |year=2006 |pmid=16765759 |doi=10.1016/S0140-6736(06)68845-4}}</ref>
Warfarin treatment requires frequent monitoring with a blood test called the [[Prothrombin time|international normalized ratio]] (INR); this determines whether the correct dose is being used. In atrial fibrillation, the usual target INR is between 2.0 and 3.0 (higher targets are used in patients with mechanical [[artificial heart valve]]s, many of whom may also have atrial fibrillation). A high INR may indicate increased bleeding risk, while a low INR would indicate that there is insufficient protection from stroke.
An attempt was made to find a better method of implementing warfarin therapy without the inconvenience of regular monitoring and risk of intracranial hemorrhage. A combination of aspirin and fixed-dose warfarin (initial INR 1.2-1.5) was tried. Unfortunately, in a study of AF patients with additional risk factors for thromboembolism, the combination of aspirin and the lower dose of warfarin was significantly inferior to the standard adjusted-dose warfarin (INR 2.0-3.0), yet still had a similar risk of intracranial hemorrhage.<ref>{{cite journal | title=Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial | journal=Lancet | volume=348 | issue=9028 | pages=633–638 | year=1996 |url=http://www.thelancet.com/journals/lancet/article/PIIS0140673696034873/abstract | pmid=8782752 | doi=10.1016/S0140-6736(96)03487-3}}</ref>
===Elderly patients===
The very elderly (patients aged 75 years or more) may benefit from anticoagulation provided that their anticoaguation does not increase hemorrhagic complications, which is a difficult goal. Patients aged 80 years or more may be especially susceptible to bleeding complications, with a rate of 13 bleeds per 100 person-years.<ref name="pmid17515465">{{cite journal |author=Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S |title=Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation |journal=Circulation |volume=115 |issue=21 |pages=2689-96 |year=2007 |pmid=17515465 |doi=10.1161/CIRCULATIONAHA.106.653048}}</ref> A rate of 13 bleeds per 100 person years would seem to preclude use of warfarin; however, a [[randomized controlled trial]] found benefit in treating patients 75 years or over with a [[number needed to treat]] of 50.<ref name="pmidpendingMant"> {{cite journal |author=Mant J et al |title=Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial |journal=Lancet |volume=370 |issue= |pages=493-503 | year=2007 |pmid= |doi=10.1016/S0140-6736(07)61233-1}}</ref> Of note, this study had very low rate of hemorrhagic complications in the warfarin group.
===Rate control versus rhythm control===
AF can cause disabling and annoying symptoms. [[Palpitations]], [[Angina pectoris|angina]], lassitude (weariness), and decreased exercise tolerance are related to rapid heart rate and inefficient cardiac output caused by AF. Furthermore, AF with a persistent rapid rate can cause a form of [[heart failure]] called [[tachycardia induced cardiomyopathy]]. This can significantly increase mortality and morbidity, which can be prevented by early and adequate treatment of the AF.
There are two ways to approach these symptoms: rate control and rhythm control. ''Rate control'' treatments seek to reduce the heart rate to normal, usually 60 to 100 beats per minute. ''Rhythm control'' seeks to restore the normal heart rhythm, called normal sinus rhythm. Studies suggest that rhythm control is mainly a concern in newly diagnosed AF, while rate control is more important in the chronic phase. Rate control with anticoagulation is as effective a treatment as rhythm control in long term mortality studies, the AFFIRM Trial.<ref name=pmid12466506>{{cite journal | author=Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, Corley SD | title=A comparison of rate control and rhythm control in patients with atrial fibrillation | journal=N Engl J Med | year=2002 | pages=1825-33 | volume=347 | issue=23 }} PMID 12466506</ref>
The AFFIRM study showed no difference in risk of stroke in patients who have converted to a normal rhythm with anti-arrhythmic treatment, compared to those who have only rate control.<ref name=pmid12466506/>
===Rate control===
Rate control is achieved with medications that work by increasing the degree of block at the level of the AV node, effectively decreasing the number of impulses that conduct down into the ventricles. This can be done with:<ref name="pmid16908781"/>
* [[Beta blockers]] (preferably the "cardioselective" beta blockers such as [[metoprolol]], [[atenolol]], [[bisoprolol]])
* [[Cardiac glycosides]] (i.e. [[digoxin]])
* [[Calcium channel blocker]]s (i.e. [[diltiazem]] or [[verapamil]])
In addition to these agents, [[amiodarone]] has some AV node blocking effects (particularly when administered intravenously), and can be used in individuals when other agents are contraindicated or ineffective (particularly due to hypotension).
====Cardioversion====
{{main|Cardioversion}}
Rhythm control methods include electrical and chemical [[cardioversion]]:<ref name="pmid16908781"/>
* ''Electrical cardioversion'' involves the restoration of normal heart rhythm through the application of a DC electrical shock.
* ''Chemical cardioversion'' is performed with drugs, such as [[amiodarone]], [[dronedarone]]<ref>{{cite journal |author=Singh BN, Connolly SJ, Crijns HJ, ''et al'' |title=Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter |journal=N. Engl. J. Med. |volume=357 |issue=10 |pages=987–99 |year=2007 |pmid=17804843 |doi=10.1056/NEJMoa054686}}</ref>, [[procainamide]], [[ibutilide]], [[propafenone]] or [[flecainide]].
The main risk of cardioversion is systemic embolization of a [[thrombus]] (blood clot) from the previously fibrillating left atrium. Cardioversion should not be performed without adequate anticoagulation in patients with more than 48 hours of atrial fibrillation. Cardioversion may be performed in instances of AF lasting more than 48 hours if a [[transesophogeal echocardiogram]] (TEE) demonstrates no evidence of clot within the heart.<ref name="pmid16908781"/>
Whichever method of cardioversion is used, approximately 50% of patient [[relapse]] within one year, although the continued daily use of oral antiarrhythmic drugs may extend this period. The key risk factor for relapse is duration of AF, although other risk factors that have been identified include the presence of structural heart disease, and increasing age.
===Maintenance of sinus rhythm===
The mainstay of maintaining sinus rhythm is the use of antiarrhythmic agents. Recently, other approaches have been developed that promise to decrease or eliminate the need for antiarrhythmic agents.
====Antiarrhythmic agents====
{{main|Antiarrhythmic agent}}
The [[antiarrhythmic agent|anti-arrhythmic medications]] often used in either pharmacological cardioversion or in the prevention of relapse to AF alter the flux of ions in heart tissue, making them less excitable, setting the stage for spontaneous and durable cardioversion. These medications are often used in concert with electrical cardioversion.
==Invasive treatment of atrial fibrillation==
==Invasive treatment of atrial fibrillation==
Revision as of 15:25, 15 June 2009
Conduction
Sinus rhythm
Atrial fibrillation
Atrial fibrillation
The P waves, which represent depolarization of the atria, are irregular or absent during atrial fibrillation.
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In patients with AF where rate control drugs are ineffective and it is not possible to restore sinus rhythm using cardioversion, non-pharmacological alternatives are available. For example, to control rate it is possible to destroy the bundle of cells connecting the upper and lower chambers of the heart - the atrioventricular node - which regulates heart rate, and to implant a pacemaker instead. A more complex technique, which avoids the need for a pacemaker, involves ablating groups of cells near the pulmonary veins where atrial fibrillation is thought to originate, or creating more extensive lesions in an attempt to prevent atrial fibrillation from establishing itself.[1]
Ablation is a newer technique and has shown some promise for cases of recurrent AF that are unresponsive to conventional treatments. Radiofrequency ablation (RFA) uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue. The energy emitting probe (electrode) is placed into the heart through a catheter inserted into veins in the groin or neck. Electrodes that can detect electrical activity from inside the heart are also inserted, and the electrophysiologist uses these to "map" an area of the heart in order to locate the abnormal electrical activity before eliminating the responsible tissue.
Most AF ablations consist of isolating the electrical pathways from the pulmonary veins (PV)[2], which are located on the posterior wall of the left atrium. All other veins from the body (including neck and groin) lead to the right atrium, so in order to get to the left atrium the catheters must get across the atrial septum. This is done by piercing a small hole in the septal wall. This is called a transseptal approach. Once in the left atrium, the physician may perform Wide Area Circumferential Ablation (WACA) to electrically isolate the PVs from the left atrium.[3]
Some more recent approaches to ablating AF is to target sites that are particularly disorganized in both atria as well as in the coronary sinus (CS). These sites are termed complex fractionated atrial electrogram (CFAE) sites.[4]. It is believed by some that the CFAE sites are the cause of AF, or a combination of the PVs and CFAE sites are to blame. New techniques include the use of cryoablation (tissue freezing using a coolant which flows through the catheter), microwave ablation, where tissue is ablated by the microwave energy "cooking" the adjacent tissue, and high intensity focused ultrasound (HIFU), which destroys tissue by heating. This is an area of active research, especially with respect to the RF ablation technique and emphasis on isolating the pulmonary veins that enter into the left atrium.
Efficacy and risks of catheter ablation of atrial fibrillation are areas of active debate. A worldwide survey of the outcomes of 8745 ablation procedures[5] demonstrated a 52% success rate (ranging from 14.5% to 76.5% among centers), with an additional 23.9% of patients becoming asymptomatic with addition of an antiarrhythmic medication. In 27.3% of patients, more than one procedure was required to attain these results. There was at least one major complication in 6% of patients. A thorough discussion of results of catheter ablation was published in 2007[6]; it notes that results are widely variable, due in part to differences in technique, follow-up, definitions of success, use of antiarrhythmic therapy, and in experience and technical proficiency.
James Cox, MD, and associates developed the Cox maze procedure, an open-heart surgical procedure intended to eliminate atrial fibrillation, and performed the first one in 1987. "Maze" refers to the series of incisions made in the atria, which are arranged in a maze-like pattern. The intention was to eliminate AF by using incisional scars to block abnormal electrical circuits (atrial macro reentry) that AF requires. This procedure required an extensive series of endocardial (from the inside of the heart) incisions through both atria, a median sternotomy (vertical incision through the breastbone) and cardiopulmonary bypass (heart-lung machine). A series of improvements were made, culminating in 1992 in the Cox maze III procedure, which is now considered to be the "gold standard" for effective surgical cure of AF. The Cox maze III is sometimes referred to as the "traditional maze", the "cut and sew maze", or simply the "maze".[7]
Minimaze surgery is minimally invasive cardiac surgery similarly intended to cure atrial fibrillation. The "Minimaze" procedure refers to "mini" versions of the original maze procedure. These procedures are less invasive than the Cox maze procedure and do not require a median sternotomy (vertical incision in the breastbone) or cardiopulmonary bypass (heart-lung machine). These procedures use microwave, radiofrequency, or acoustic energy to ablate atrial tissue near the pulmonary veins.
Prognosis
Follow up & Secondary prevention
Risk factors for ischemic stroke or systemic embolization in patient with non valvular atrial fibrillation
Results from the Pulmonary Vein Antrum Isolation versus AV Node Ablation with Bi-Ventricular Pacing for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure (PABA-CHF) study suggest that pulmonary-vein (PV) isolation leads to better morphologic and functional results than atrioventricular (AV) node ablation with biventricular pacing for congestive heart failure (CHF) in patients with atrial fibrillation.
In this prospective, multicenter study, 41 patients were randomized to PV isolation and 40 to AV node ablation with biventricular pacing. At 6 months, patients in the PV isolation group had higher mean ejection fractions (35% vs 29%, p<0.001), greater 6 minute distances walked (340 vs 297 meters, p <0.001), and better quality of life scores as determined by the Minnesota Living with Heart Failure questionnaire (60 vs 82, p<0.001, where lower scores indicate better quality of life) than those in the AV node ablation arm.
These PABA-CHF study findings thus suggest the potential advantages of performing PV isolation over AV node ablation with biventricular pacing for this patient population.
Noted limitations of the study include using sites with extensive experience in performing ablations, an unblinded study design, and a relatively short follow-up time. (NEJM by Mohammed N. Khan, et al.)
↑Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T. (2004). "A new approach for catheter ablation of atrial fibrillation: mapping of the electrophysiologic substrate". J Am Coll Cardiol. 43 (11): 2044–53. doi:10.1016/j.jacc.2003.12.054. PMID15172410.CS1 maint: Multiple names: authors list (link)
↑Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, Kim YH, Klein G, Packer D, Skanes A. (2005). "Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation". Circulation. 111: 1100–1105. doi:10.1161/01.CIR.0000157153.30978.67. PMID15723973.CS1 maint: Multiple names: authors list (link)
↑Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H, Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ. (2007). "HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and surgical ablation of atrial fibrillation". Heart Rhythm. 4 (6): 816–61. PMID17556213.CS1 maint: Multiple names: authors list (link)
↑Cox JL, Schuessler RB, Lappas DG, Boineau JP (1996). "An 8 1/2-year clinical experience with surgery for atrial fibrillation". Ann. Surg. 224 (3): 267–73, discussion 273-5. PMID8813255.CS1 maint: Multiple names: authors list (link)
↑Estes NAM 3rd, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS, McNamara RL, Messer JV, Ritchie JL, Romeo SJW, Waldo AL, Wyse DG. ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with non valvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Performance Measures for Atrial Fibrillation). Circulation 2008; 117:1101–1120
Further Readings
Fuster V, Rydén LE, Cannom DS, et al (2006). "ACC/AHA/ESC 2006 Guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society". Circulation 114 (7): e257-354. doi:10.1161/CIRCULATIONAHA.106.177292. PMID 16908781.
Estes NAM 3rd, Halperin JL, Calkins H, Ezekowitz MD, Gitman P, Go AS, McNamara RL, Messer JV, Ritchie JL, Romeo SJW, Waldo AL, Wyse DG. ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with non valvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Performance Measures for Atrial Fibrillation). Circulation 2008; 117:1101–1120
Braunwald's Heart Disease, Libby P, 8th ed., 2007, ISBN 978-1-41-604105-4
Hurst's the Heart, Fuster V, 12th ed. 2008, ISBN 978-0-07-149928-6
Willerson JT, Cardiovascular Medicine, 3rd ed., 2007, ISBN 978-1-84628-188-4
