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1. What are the differences between lone, paroxysmal, persistent and permanent atrial fibrillation (AF)?
A joint task force met in 2001 to develop guidelines for the management of AF and proposed a clinically relevant classification system ADDIN EN.CITE Fuster20011011673357104172001Oct 23ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology2118-50Fuster, V.Ryden, L. E.Asinger, R. W.Cannom, D. S.Crijns, H. J.Frye, R. L.Halperin, J. L.Kay, G. N.Klein, W. W.Levy, S.McNamara, R. L.Prystowsky, E. N.Wann, L. S.Wyse, D. G.Gibbons, R. J.Antman, E. M.Alpert, J. S.Faxon, D. P.Gregoratos, G.Hiratzka, L. F.Jacobs, A. K.Russell, R. O.Smith, S. C., Jr.Alonso-Garcia, A.Blomstrom-Lundqvist, C.de Backer, G.Flather, M.Hradec, J.Oto, A.Parkhomenko, A.Silber, S.Torbicki, A.CirculationAgedAged, 80 and overAlgorithmsAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/classification/*diagnosis/epidemiology/*therapyAtrial Flutter/diagnosisComorbidityContinental Population GroupsDiagnosis, DifferentialDisease ManagementElectric CountershockElectrocardiographyFemaleFibrinolytic Agents/therapeutic useHumansMaleMiddle AgedPrevalencePrognosisRisk AssessmentTachycardia/diagnosisThromboembolism/etiology/prevention & controlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11673357[1]. Episodes of AF that occur on more than one occasion are called recurrent. Paroxysmal AF is used to identify AF that generally last less than or equal to 7 days and may be recurrent. Persistent AF refers to episodes that last longer than 7 days. If AF continues for over a year, with or without failed cardioversion, it is called Persistent. The presence or absence of symptoms do not affect the classification of AF. This system of classification excludes AF that lasts less than 30 seconds or that is secondary to a precipitating condition, such as surgery or myocardial infarction. The term Chronic AF is not used in this classification, but is generally what is thought of as Permanent AF. Lone AF refers to AF that occurs in the absence of echocardiographic or clinical evidence of cardiopulmonary disease and generally applies to patients less than 60 years old and implies a group of patients at low risk of thromboembolic events. Lone AF can be paroxysmal, persistent or permanent.
2. What diagnostic tests should be done in patients with a new diagnosis of atrial fibrillation?
There are multiple risk factors and disease processes that have been associated with atrial fibrillation. A study of the Framingham cohort, for example, revealed that diabetes, hypertension, myocardial infarction and age are strong risk factors of AF ADDIN EN.CITE Benjamin1994208114238271111994Mar 16Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study840-4Framingham Heart Study, MA 01701.Benjamin, E. J.Levy, D.Vaziri, S. M.D'Agostino, R. B.Belanger, A. J.Wolf, P. A.JamaAge FactorsAgedAged, 80 and overAtrial Fibrillation/*epidemiologyCausalityCohort StudiesDiabetes ComplicationsFemaleHeart Failure, Congestive/complicationsHeart Valve Diseases/complicationsHumansHypertension/complicationsLogistic ModelsMaleMiddle AgedMultivariate AnalysisResearch Support, U.S. Gov't, P.H.S.Risk FactorsSex Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8114238[2]. Tests should be directed at determining underlying etiology or an associated, treatable condition. A thorough history may reveal symptoms of cardiopulmonary disease or expose risk factors such as binge drinking. Physical exam can assess blood pressure and heart murmurs and signs of heart failure. The electrocardiogram can help establish the diagnosis of AF and assess for ventricular hypertrophy and acute myocardial infarction. Echocardiography should be performed to rule out ventricular dysfunction, valvular disease, rheumatic heart disease and hypertrophic cardiomyopathy. Patients should also be screened for diabetes, if not already established, with fasting blood sugars. Although TSH is routinely checked, a Canadian study revealed that fewer than 1% of patients with newly diagnosed AF were found by two years to have clinical hyperthyroidism and that checking TSH routinely is of low yield ADDIN EN.CITE Krahn1996308885821156191996Oct 28How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators2221-4University of Western Ontario, London.Krahn, A. D.Klein, G. J.Kerr, C. R.Boone, J.Sheldon, R.Green, M.Talajic, M.Wang, X.Connolly, S.Arch Intern MedAtrial Fibrillation/blood/*etiology/physiopathologyEvaluation StudiesFemaleHumansLogistic ModelsMaleMiddle AgedResearch Support, Non-U.S. Gov'tRisk FactorsThyroid Diseases/blood/*complications*Thyroid Function TestsThyrotropin/bloodTime Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8885821[3]. Further targeted testing should be performed if clinical suspicion exists for acute myocardial infarction, obstructive sleep apnea, COPD or pulmonary embolism.
3. What are the indications for hospitalization in a patient with atrial fibrillation?
Under appropriate conditions, it is safe to manage even new onset AF as an outpatient. Admission to the hospital is often considered in order to rule out acute myocardial infarction. In one study of 109 patients who were admitted with new onset AF to rule out myocardial infarction, only 5.5% ruled in ADDIN EN.CITE Zimetbaum200040110284743642000OctIncidence and predictors of myocardial infarction among patients with atrial fibrillation1223-7Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA. pzimetba@caregroup.harvard.eduZimetbaum, P. J.Josephson, M. E.McDonald, M. J.McClennen, S.Korley, V.Ho, K. K.Papageorgiou, P.Cohen, D. J.J Am Coll CardiolAgedAtrial Fibrillation/complications/*diagnosis/epidemiologyChest Pain/diagnosis/epidemiology/etiologyComparative StudyDiagnosis, Differential*ElectrocardiographyFemaleHumansIncidenceMaleMyocardial Infarction/*diagnosis/epidemiology/etiologyPrognosisProspective StudiesResearch Support, Non-U.S. Gov'tRisk FactorsSensitivity and Specificityhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11028474[4]. In this study, all patients who lacked ST depressions > 2mm or ST elevations ruled out for a myocardial infarct. It would be reasonable to treat those patients at low risk for an acute coronary syndrome as outpatients. If the patient, however, demonstrates hemodynamic instability, signs or symptoms of heart failure, persistent rapid ventricular response or symptoms that can not be controlled in the emergency room, he or she should be admitted for further management and potential inpatient cardioversion. Although not yet validated for these purposes, a model for calculating risk of stroke or death, such as the one based on the Framingham cohort ADDIN EN.CITE Wang2003601294167729082003Aug 27A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study1049-56Framingham Heart Study, Framingham, MA 01702-5827, USA.Wang, T. J.Massaro, J. M.Levy, D.Vasan, R. S.Wolf, P. A.D'Agostino, R. B.Larson, M. G.Kannel, W. B.Benjamin, E. J.JamaAgedAged, 80 and overAnticoagulants/therapeutic useAtrial Fibrillation/*complications/drug therapyCerebrovascular Accident/*epidemiology/*etiology/prevention & controlFemaleHumansMaleMiddle AgedProportional Hazards ModelsResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Risk AssessmentSurvival AnalysisWarfarin/therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12941677[5], could potentially be used to help decide which patients would best be served as inpatients.
4. Is rhythm control better than rate control?
It was formerly believed that maintenance of AV synchrony was beneficial and was often attained at considerable cost. The largest randomized controlled trial that challenged this assumption was the AFFIRM trial ADDIN EN.CITE Wyse20027012466506347232002Dec 5A comparison of rate control and rhythm control in patients with atrial fibrillation1825-33AFFIRM Clinical Trial Center, Axio Research, 2601 4th Ave., Ste. 200, Seattle, WA 98121, USA.Wyse, D. G.Waldo, A. L.DiMarco, J. P.Domanski, M. J.Rosenberg, Y.Schron, E. B.Kellen, J. C.Greene, H. L.Mickel, M. C.Dalquist, J. E.Corley, S. D.N Engl J MedAdrenergic beta-Antagonists/therapeutic useAgedAmiodarone/therapeutic useAnti-Arrhythmia Agents/adverse effects/*therapeutic useAtrial Fibrillation/complications/mortality/*therapyCalcium Channel Blockers/therapeutic useCatheter AblationCerebrovascular Accident/etiologyCombined Modality TherapyComparative StudyCross-Over Studies*Electric CountershockFemaleHeart RateHumansMaleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Survival Analysishttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12466506[6]. 4060 patients with asymptomatic AF were randomized to rate control with nodal agents versus rhythm control with pharmacologic or electrical cardioversion. There were no statistically significant differences in stroke or death between the two groups. However, patients in the rhythm control group had more hospitalizations and adverse drug reactions and many deaths in the rhythm control group may have been attributed to the antiarrhythmic drugs themselves. Similar findings were noted in the RACE trial, a randomized controlled trial with 522 participants ADDIN EN.CITE Van Gelder20028012466507347232002Dec 5A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation1834-40Department of Cardiology, Thoraxcenter, University Hospital, Groningen, The Netherlands. i.c.van.gelder@thorax.azg.nl.Van Gelder, I. C.Hagens, V. E.Bosker, H. A.Kingma, J. H.Kamp, O.Kingma, T.Said, S. A.Darmanata, J. I.Timmermans, A. J.Tijssen, J. G.Crijns, H. J.N Engl J MedAdrenergic beta-Antagonists/therapeutic useAgedAnti-Arrhythmia Agents/*therapeutic useAnticoagulants/*therapeutic useAtrial Fibrillation/complications/mortality/*therapyCalcium Channel Blockers/therapeutic useCombined Modality TherapyComparative StudyDisease-Free Survival*Electric CountershockFemaleHeart RateHumansHypertension/complicationsMaleRecurrenceResearch Support, Non-U.S. Gov'tSex Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12466507[7]. It is reasonable, however, to aim for rhythm control in patients who either can not achieve adequate rate control or are symptomatic from AF, especially in the younger population that was not well represented in these trials. As newer, potentially safer approaches to rhythm control become available, such as catheter ablation techniques, the benefits of one approach over the other will need to be readdressed.
5. Are beta blockers better than calcium channel blockers for rate control?
Although rate control has been established as an appropriate approach to the management of AF in older, asymptomatic patients, the choice of which nodal agent to use is in question. The goals for patients randomized to rate control in the AFFIRM trial was a heart rate below 80 at rest and below 110 during a six minute walk test ADDIN EN.CITE Wyse20027012466506347232002Dec 5A comparison of rate control and rhythm control in patients with atrial fibrillation1825-33AFFIRM Clinical Trial Center, Axio Research, 2601 4th Ave., Ste. 200, Seattle, WA 98121, USA.Wyse, D. G.Waldo, A. L.DiMarco, J. P.Domanski, M. J.Rosenberg, Y.Schron, E. B.Kellen, J. C.Greene, H. L.Mickel, M. C.Dalquist, J. E.Corley, S. D.N Engl J MedAdrenergic beta-Antagonists/therapeutic useAgedAmiodarone/therapeutic useAnti-Arrhythmia Agents/adverse effects/*therapeutic useAtrial Fibrillation/complications/mortality/*therapyCalcium Channel Blockers/therapeutic useCatheter AblationCerebrovascular Accident/etiologyCombined Modality TherapyComparative StudyCross-Over Studies*Electric CountershockFemaleHeart RateHumansMaleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Survival Analysishttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12466506[6]. In a sub-study of the AFFIRM trial, the medical approach to rate control was evaluated ADDIN EN.CITE Olshansky200490150634304372004Apr 7The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation1201-8University of Iowa, Iowa City, Iowa 52242, USA. brian-olshansky@uiowa.eduOlshansky, B.Rosenfeld, L. E.Warner, A. L.Solomon, A. J.O'Neill, G.Sharma, A.Platia, E.Feld, G. K.Akiyama, T.Brodsky, M. A.Greene, H. L.J Am Coll CardiolAdrenergic beta-Antagonists/therapeutic useAgedAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/*physiopathology/therapyCalcium Channel Blockers/therapeutic useCatheter AblationComparative StudyDigoxin/therapeutic useDrug Therapy, CombinationElectrocardiography, AmbulatoryFemaleFollow-Up StudiesHeart Rate/drug effects/*physiologyHumansMaleMiddle AgedMultivariate AnalysisPacemaker, ArtificialResearch Support, U.S. Gov't, P.H.S.Stroke Volume/drug effects/physiologyTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15063430[8]. Patients whose first drug was a beta-blocker, with or without digoxin, were able to achieve rate control in 70% of cases whereas those whose first drug was a calcium channel blocker, with or without digoxin, were successful in 54% of cases. Calcium channel blockers may, however, be more beneficial in selected groups, such as those prone to bronchospasm or who develop other adverse reactions to beta blockers or younger patients who may have diminished exercise capacity with beta blockers. Six minute walk tests or Holter monitoring during activities of daily living may be necessary to assess adequate rate control.
6. Which patients benefit from treatment with digoxin?
Among its many mechanisms of action, digoxin increases vagal tone and can have a direct sympathoinhibitory effect. Because it has been available for a long time, it is relatively inexpensive and requires only once a day administration, it remains a popular therapeutic agent. Alone, it is effective at rate control as a first-line agent in only 58% of patients, which is comparable to calcium channel blockers but worse than beta blockers alone ADDIN EN.CITE Olshansky200490150634304372004Apr 7The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation1201-8University of Iowa, Iowa City, Iowa 52242, USA. brian-olshansky@uiowa.eduOlshansky, B.Rosenfeld, L. E.Warner, A. L.Solomon, A. J.O'Neill, G.Sharma, A.Platia, E.Feld, G. K.Akiyama, T.Brodsky, M. A.Greene, H. L.J Am Coll CardiolAdrenergic beta-Antagonists/therapeutic useAgedAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/*physiopathology/therapyCalcium Channel Blockers/therapeutic useCatheter AblationComparative StudyDigoxin/therapeutic useDrug Therapy, CombinationElectrocardiography, AmbulatoryFemaleFollow-Up StudiesHeart Rate/drug effects/*physiologyHumansMaleMiddle AgedMultivariate AnalysisPacemaker, ArtificialResearch Support, U.S. Gov't, P.H.S.Stroke Volume/drug effects/physiologyTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15063430[8]. In combination, it can help reduce the dose of calcium channel blocker or beta blocker required to achieve rate control and together with carvedilol, can lower the heart rate better than either agent alone in patients with systolic heart failure ADDIN EN.CITE Khand20031001466225742112003Dec 3Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?1944-51Academic Unit of Cardiology, University of Hull, Kingston-Upon-Hull, United Kingdom.Khand, A. U.Rankin, A. C.Martin, W.Taylor, J.Gemmell, I.Cleland, J. G.J Am Coll CardiolAdrenergic beta-Antagonists/*administration & dosageAgedAnti-Arrhythmia Agents/*administration & dosageAtrial Fibrillation/complications/*drug therapyComparative StudyDigoxin/*administration & dosageDouble-Blind MethodDrug Therapy, CombinationElectrocardiography, AmbulatoryExercise TestFemaleHeart Failure, Congestive/complications/*drug therapyHumansMaleMonoterpenes/*administration & dosageResearch Support, Non-U.S. Gov'thttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14662257[9]. In the absence of heart failure, digoxin is not effective at converting patients in AF to sinus rhythm ADDIN EN.CITE Falk1987110354852110641987AprDigoxin for converting recent-onset atrial fibrillation to sinus rhythm. A randomized, double-blinded trial503-6Falk, R. H.Knowlton, A. A.Bernard, S. A.Gotlieb, N. E.Battinelli, N. J.Ann Intern MedAtrial Fibrillation/*drug therapy/physiopathologyClinical TrialsDigoxin/blood/*therapeutic useDouble-Blind MethodHeart Rate/drug effectsHumansMiddle AgedMyocardial Contraction/drug effectsRandom AllocationResearch Support, Non-U.S. Gov'tStroke Volume/drug effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3548521[10], but may reduce the frequency of symptomatic episodes in paroxysmal AF. In summary, digoxin may benefit patients already on calcium channel blockers or beta blockers who have not achieved adequate rate control, especially those with heart failure, and patients with frequent episodes of symptomatic paroxysmal AF.
7. Is pharmacologic cardioversion better than electrical cardioversion in patients who need rhythm control?
There are no trials that have randomized patients undergoing acute rhythm control to pharmacologic versus electrical cardioversion. The decision remains primarily the preference of the patient and health care provider. Electrical cardioversion with a biphasic waveform is effective in 80-90% of cases ADDIN EN.CITE Page20021201208459439122002Jun 19Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial1956-63Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9047, USA. rpage@parknet.pmh.orgPage, R. L.Kerber, R. E.Russell, J. K.Trouton, T.Waktare, J.Gallik, D.Olgin, J. E.Ricard, P.Dalzell, G. W.Reddy, R.Lazzara, R.Lee, K.Carlson, M.Halperin, B.Bardy, G. H.J Am Coll CardiolAdultAgedAged, 80 and overAtrial Fibrillation/*therapyComparative StudyDouble-Blind MethodElectric Countershock/*methodsFemaleHumansMaleMiddle AgedResearch Support, Non-U.S. Gov'tTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12084594[11], but requires conscious sedation. A small group of patients may be at risk of developing VT, particularly in the setting of hypokalemia or digitalis intoxication. The efficacy of pharmacologic therapy varies depending on the agent chosen, but is generally not as high as electrical cardioversion. Pharmacologic cardioversion tends to be tolerated, but the risk of torsade de pointes can range from 1% 8% , depending on the agent and dose used as well as any underlying susceptibilities, such as bradycardia and hypokalemia ADDIN EN.CITE Roden19941308065408331121994Sep 22Risks and benefits of antiarrhythmic therapy785-91Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232-6602.Roden, D. M.N Engl J MedAnti-Arrhythmia Agents/adverse effects/*therapeutic useArrhythmia/*drug therapy/mortalityElectrocardiography/drug effectsHumansRiskTorsades de Pointes/chemically inducedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8065408[12]. The primary risk of cardioversion with either approach remains thromboembolism or stroke and can be as high as 7% in those not adequately anticoagulated. The risk does not differ significantly between these two approaches.
8. How should electrical cardioversion be performed?
Unless the patient is hemodynamically unstable or there is another indication for emergent cardioversion, the patient should undergo conscious sedation. A recent multicenter controlled trial randomized 203 patients to either biphasic or monophasic shock waveforms and found that biphasic shocks were more efficacious, requiring fewer shocks and resulted in less dermal injury ADDIN EN.CITE Page20021201208459439122002Jun 19Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial1956-63Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9047, USA. rpage@parknet.pmh.orgPage, R. L.Kerber, R. E.Russell, J. K.Trouton, T.Waktare, J.Gallik, D.Olgin, J. E.Ricard, P.Dalzell, G. W.Reddy, R.Lazzara, R.Lee, K.Carlson, M.Halperin, B.Bardy, G. H.J Am Coll CardiolAdultAgedAged, 80 and overAtrial Fibrillation/*therapyComparative StudyDouble-Blind MethodElectric Countershock/*methodsFemaleHumansMaleMiddle AgedResearch Support, Non-U.S. Gov'tTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12084594[11]. The amount of energy necessary for cardioversion varies depending on the waveform used, duration of AF and size of patient. For monophasic waveforms, the minimal therapy should be 100J for < 48h, 150J for < 7 days and 200J for >1 year. For biphasic waveforms, the minimal initial therapy should be 50J for < 48h, 100J for < 7 days and 150J for > 1year. This can be titrated up to the maximum energy of 360J for monophasic and 200J for biphasic waveforms. Anterior-posterior paddle positioning, over the sternum and left scapula, is more effective than the anterior-lateral approach ADDIN EN.CITE Botto1999140105735028261999DecExternal cardioversion of atrial fibrillation: role of paddle position on technical efficacy and energy requirements726-30Department of Cardiology, Ospedale "Sant' Anna", Via Napoleona 60, 22100 Como, Italy. ccaec@tin.itBotto, G. L.Politi, A.Bonini, W.Broffoni, T.Bonatti, R.HeartAdultAgedAged, 80 and overAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/drug therapy/*therapyCombined Modality TherapyComparative StudyElectric Countershock/*methodsFemaleHumansMaleMiddle AgedProspective StudiesTime FactorsTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10573502[13]. Cardioversion in patients with pacemakers and defibrillators is safe, but devices should be interrogated immediately before and after external discharge. Long-term success improves if the cardioversion is performed after the inciting cause, if any, of AF has resolved and after initiation of therapy for maintenance of sinus rhythm.
9. Which antiarrhythmic agents should be used for acute conversion to and maintenance of sinus rhythm?
The choice of antiarrhythmic agent depends primarily on the presence or absence of any underlying cardiovascular disease, the side effect profile and the experience of the clinician with certain agents. There are few studies that have randomized patients to the different available drugs. In a meta-analysis of clinical trials measuring efficacy of pharmacologic cardioversion, it was found that ibutilide, dofetilide and flecainide were 24-29 times more likely to lead to cardioversion than standard therapy with calcium channel or beta blockers ADDIN EN.CITE Miller20001501109357049112000NovEfficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials1033-46Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. mmiller@ahrq.govMiller, M. R.McNamara, R. L.Segal, J. B.Kim, N.Robinson, K. A.Goodman, S. N.Powe, N. R.Bass, E. B.J Fam PractAgedAnti-Arrhythmia Agents/adverse effects/*therapeutic useAtrial Fibrillation/*drug therapyEvidence-Based MedicineHumansMiddle AgedRandomized Controlled TrialsResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11093570[14]. Although amiodarone and propafenone were moderately effective, sotalol was generally ineffective at inducing sinus rhythm. In this meta-analysis, all agents were approximately equally efficacious in the maintenance of normal sinus rhythm. Given the propensity of certain agents to induce ventricular arrhythmias in the presence of cardiovascular disease, guidelines from the joint task force recommend that for maintenance of sinus rhythm, flecainide, propafenone and sotalol be used as first-line agents in patients with no or minimal cardiovascular disease ADDIN EN.CITE Fuster20011011673357104172001Oct 23ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology2118-50Fuster, V.Ryden, L. E.Asinger, R. W.Cannom, D. S.Crijns, H. J.Frye, R. L.Halperin, J. L.Kay, G. N.Klein, W. W.Levy, S.McNamara, R. L.Prystowsky, E. N.Wann, L. S.Wyse, D. G.Gibbons, R. J.Antman, E. M.Alpert, J. S.Faxon, D. P.Gregoratos, G.Hiratzka, L. F.Jacobs, A. K.Russell, R. O.Smith, S. C., Jr.Alonso-Garcia, A.Blomstrom-Lundqvist, C.de Backer, G.Flather, M.Hradec, J.Oto, A.Parkhomenko, A.Silber, S.Torbicki, A.CirculationAgedAged, 80 and overAlgorithmsAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/classification/*diagnosis/epidemiology/*therapyAtrial Flutter/diagnosisComorbidityContinental Population GroupsDiagnosis, DifferentialDisease ManagementElectric CountershockElectrocardiographyFemaleFibrinolytic Agents/therapeutic useHumansMaleMiddle AgedPrevalencePrognosisRisk AssessmentTachycardia/diagnosisThromboembolism/etiology/prevention & controlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11673357[1]. According to these guidelines, patients with heart failure can be started on amiodarone or dofetilide, patients with coronary disease can begin with sotalol and patients with hypertension can be started on amiodarone.
10. How is amiodarone used in the management of AF?
Amiodarone is a class III agent whose use in AF, although not FDA approved for this indication, has become exceedingly common primarily because of its low risk of ventricular arrhythmias compared with other antiarrhythmics and lack of negative ionotropic effects. The major deterrent is that its long-term use is associated with multiple toxicities, namely pulmonary, hepatic and thyroid toxicities and its use in younger populations should be limited. Although there is no standardized dosing regimen, consensus guidelines recommend an initial loading of approximately 10 grams of amiodarone and subsequent titration down to 200mg daily ADDIN EN.CITE Fuster20011011673357104172001Oct 23ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology2118-50Fuster, V.Ryden, L. E.Asinger, R. W.Cannom, D. S.Crijns, H. J.Frye, R. L.Halperin, J. L.Kay, G. N.Klein, W. W.Levy, S.McNamara, R. L.Prystowsky, E. N.Wann, L. S.Wyse, D. G.Gibbons, R. J.Antman, E. M.Alpert, J. S.Faxon, D. P.Gregoratos, G.Hiratzka, L. F.Jacobs, A. K.Russell, R. O.Smith, S. C., Jr.Alonso-Garcia, A.Blomstrom-Lundqvist, C.de Backer, G.Flather, M.Hradec, J.Oto, A.Parkhomenko, A.Silber, S.Torbicki, A.CirculationAgedAged, 80 and overAlgorithmsAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/classification/*diagnosis/epidemiology/*therapyAtrial Flutter/diagnosisComorbidityContinental Population GroupsDiagnosis, DifferentialDisease ManagementElectric CountershockElectrocardiographyFemaleFibrinolytic Agents/therapeutic useHumansMaleMiddle AgedPrevalencePrognosisRisk AssessmentTachycardia/diagnosisThromboembolism/etiology/prevention & controlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11673357[1]. One approach is to begin an oral load with 400mg twice daily for one week, followed by 200mg twice daily for two weeks, then titrated down to 200mg po daily for maintenance. Another approach proven to be safe ADDIN EN.CITE Tieleman199716090247367911997Jan 1Efficacy, safety, and determinants of conversion of atrial fibrillation and flutter with oral amiodarone53-7Department of Cardiology, University Hospital Groningen, The Netherlands.Tieleman, R. G.Gosselink, A. T.Crijns, H. J.van Gelder, I. C.van den Berg, M. P.de Kam, P. J.van Gilst, W. H.Lie, K. I.Am J CardiolAgedAmiodarone/analogs & derivatives/blood/*therapeutic useAnti-Arrhythmia Agents/*therapeutic useAtrial Fibrillation/*drug therapy/therapy/ultrasonographyAtrial Flutter/*drug therapy/therapy/ultrasonographyEchocardiographyElectric CountershockFemaleHumansMaleMiddle AgedMultivariate AnalysisProspective Studieshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9024736[15] is to load with 600mg daily for four weeks, followed by maintenance of 200mg daily. When used intravenously, amiodarone can be bolused at 150mg, followed by a drip of 1mg per hour for 6 hours and then maintained at 0.5mg per hour until the load can be completed orally. Toxicities from long-term use should be monitored with baseline and regular pulmonary function, liver function thyroid stimulating hormone tests.
11. Can antiarrhythmic agents be started as an outpatient?
Because of the risk of torsade de pointes associated with these medications, almost all studies of antiarrhythmics were performed during inpatient observation with careful monitoring for QT prolongation. In one study of 597 drug trials, 13.7% of patients suffered adverse cardiac events, including bradyarrhythmias in 8%, significant QT prolongation in 1.5% requiring drug discontinuation and ventricular arrhythmias in 1.3% of trials ADDIN EN.CITE Maisel1997190926542712741997Aug 15Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital281-4Brigham and Women's Hospital, Boston, Massachusetts, USA.Maisel, W. H.Kuntz, K. M.Reimold, S. C.Lee, T. H.Antman, E. M.Friedman, P. L.Stevenson, W. G.Ann Intern MedAdultAgedAnti-Arrhythmia Agents/*therapeutic useAtrial Fibrillation/*drug therapyElectric CountershockFemaleHumansLogistic ModelsMaleMedical RecordsMiddle AgedMultivariate AnalysisOdds RatioRetrospective StudiesRiskRisk Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9265427[16]. Some antiarrhythmics, such as dofetilide, are additionally restricted to prescribers who have completed appropriate educational forums ADDIN EN.CITE Freeland2003170150052171412 Suppl2003DecInitiation and monitoring of class III antiarrhythmic agentsS291-5From the Department of Pharmacy Services, St. Vincent Hospital and Health Services, Indianapolis, Indiana 46260, USA. safreela@stvincent.orgFreeland, S.Worthy, C.Zolnierz, M.J Cardiovasc ElectrophysiolAnti-Arrhythmia Agents/*administration & dosage/adverse effects/standardsAtrial Fibrillation/*drug therapy/nursing/*prevention & controlDrug Administration ScheduleDrug ApprovalDrug LabelingDrug Monitoring/methods/standardsDrug Therapy, Computer-Assisted/*methodsHumansPatient Care Management/*methods/standardsPatient Care TeamPhenethylamines/*administration & dosage/adverse effects/standards*Practice GuidelinesSotalol/*administration & dosage/adverse effects/standardsSulfonamides/*administration & dosage/adverse effects/standardsTorsades de Pointes/etiology/prevention & controlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15005217[17]. In one study of 129 patients with AF or flutter, subjects were given 600mg daily of amiodarone for 4 weeks and none of the patients suffered ventricular arrhythmias ADDIN EN.CITE Tieleman199718090247367911997Jan 1Efficacy, safety, and determinants of conversion of atrial fibrillation and flutter with oral amiodarone53-7Department of Cardiology, University Hospital Groningen, The Netherlands.Tieleman, R. G.Gosselink, A. T.Crijns, H. J.van Gelder, I. C.van den Berg, M. P.de Kam, P. J.van Gilst, W. H.Lie, K. I.Am J CardiolAgedAmiodarone/analogs & derivatives/blood/*therapeutic useAnti-Arrhythmia Agents/*therapeutic useAtrial Fibrillation/*drug therapy/therapy/ultrasonographyAtrial Flutter/*drug therapy/therapy/ultrasonographyEchocardiographyElectric CountershockFemaleHumansMaleMiddle AgedMultivariate AnalysisProspective Studieshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9024736[15]. Given this and similar observations, it is considered that amiodarone can be started safely on an outpatient basis.
12. What is the pill-in-pocket approach?
There are a group of patients with paroxysmal AF who have relatively mild or well tolerated symptoms during their episodes. If the episodes are infrequent enough, there may be a reluctance to initiate daily use antiarrhythmic agents. These patients may be managed with the pill-in-the-pocket approach, which consists of asking this group of patients to take a single dose of an antiarrhythmic when they become symptomatic instead of coming to the emergency room. In a study evaluating the safety of this approach ADDIN EN.CITE Alboni200420015575054351232004Dec 2Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach2384-91Division of Cardiology, Ospedale Civile, Cento, Italy. p.alboni@ausl.fe.itAlboni, P.Botto, G. L.Baldi, N.Luzi, M.Russo, V.Gianfranchi, L.Marchi, P.Calzolari, M.Solano, A.Baroffio, R.Gaggioli, G.N Engl J MedAdministration, OralAmbulatory CareAnti-Arrhythmia Agents/administration & dosage/adverseeffects/*therapeutic useAtrial Fibrillation/complications/*drug therapyFeasibility StudiesFemaleFlecainide/administration & dosage/adverse effects/*therapeutic useFollow-Up StudiesHeart Failure, Congestive/*complications/physiopathologyHumansMaleMiddle AgedPropafenone/administration & dosage/adverse effects/*therapeutic useProspective StudiesResearch Support, Non-U.S. Gov'tSelf AdministrationStroke Volumehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15575054[18], 268 patients presenting with mild or no heart disease were converted to sinus rhythm with either flecainide or propafenone in the hospital. The patients who did not have an adverse event were then followed as outpatients and advised to self-administer a single dose of flecainide or propafenone after the onset of heart palpitations. These patients had a significant fall in the number of emergency room visits and hospital admissions compared to the year prior. Only one patient experienced atrial flutter with rapid ventricular rate and 11 patients reported non-cardiac side effects. This approach is a safe option for the management of a select group of patients who would prefer not to endure long-term standing use of antiarrhythmic therapy.
13. Do angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) prevent recurrence of atrial fibrillation?
On retrospective examination of several trials, it was observed that the use of ACEI and ARBs were associated with the prevention of AF and the maintenance of sinus rhythm in patients with AF. Several potential mechanisms have been proposed and this effect is likely related to atrial remodeling as well as the modification of diseases that are associated with AF such as hypertension and congestive heart failure. In one study of 186 patients with persistent AF, participants were randomized to amiodarone versus amiodarone plus irbesartan followed by electrical cardioversion ADDIN EN.CITE Madrid20022101211924910632002Jul 16Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study331-6Arrhythmia Unit, Cardiology Department, Ramon y Cajal Hospital, Department of Medicine, Alcala University, Madrid, Spain.Madrid, A. H.Bueno, M. G.Rebollo, J. M.Marin, I.Pena, G.Bernal, E.Rodriguez, A.Cano, L.Cano, J. M.Cabeza, P.Moro, C.CirculationAdultAgedAmiodarone/adverse effects/therapeutic useAngiotensin-Converting Enzyme Inhibitors/therapeutic useAnti-Arrhythmia Agents/adverse effects/therapeutic useAtrial Fibrillation/diagnosis/*drug therapy/therapyBiphenyl Compounds/adverse effects/*therapeutic useChronic DiseaseComparative StudyElectric CountershockFemaleFollow-Up StudiesHumansKineticsMaleMiddle AgedPeriodicityReceptor, Angiotensin, Type 1Receptors, Angiotensin/*antagonists & inhibitorsRecurrenceResearch Support, Non-U.S. Gov'tTetrazoles/adverse effects/*therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12119249[19]. After 2 months, the group treated with irbesartan had fewer recurrences of AF. In a recent meta-analysis that reviewed 11 randomized trials of ACEI and ARBs that also reported new onset of AF, it was found that ACEI and ARBs reduced the relative risk of developing AF by 28% ADDIN EN.CITE Healey20052201593661545112005Jun 7Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis1832-9Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, Ontario, Canada. healeyj@hhsc.caHealey, J. S.Baranchuk, A.Crystal, E.Morillo, C. A.Garfinkle, M.Yusuf, S.Connolly, S. J.J Am Coll CardiolAngiotensin-Converting Enzyme Inhibitors/*therapeutic useAtrial Fibrillation/epidemiology/*prevention & controlComorbidityElectric CountershockHumansHypertrophy, Left Ventricular/epidemiologyRandomized Controlled TrialsReceptors, Angiotensin/*antagonists & inhibitorsVentricular Dysfunction, Left/epidemiologyhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15936615[20]. This effect was greatest in patients with heart failure. At this point there is not sufficient prospective evidence to support the empiric use of ACEI or ARBs in the treatment of AF, however, this may influence the choice of therapy in someone who also has hypertension or congestive heart failure. Larger, more definitive trials to address this question are underway.
14. Who should receive anticoagulation?
Whether or not a patient is anticoagulated depends on their risk of suffering a thromboembolic event, which is related to age and coexisting cardiovascular disease. In a large Danish cohort of patients with AF, the incidence of stroke rose from 1.3% per year in those aged 50-59 to 5.1% per year in those aged 80-89 ADDIN EN.CITE Frost20002401105943910812000JanIncident stroke after discharge from the hospital with a diagnosis of atrial fibrillation36-40Department of Cardiology, Amtssygehuset, Aarhus University Hospital, Denmark.Frost, L.Engholm, G.Johnsen, S.Moller, H.Husted, S.Am J MedAge DistributionAge of OnsetAgedAged, 80 and overAtrial Fibrillation/*complicationsCerebrovascular Accident/*epidemiology/*etiologyDenmark/epidemiologyFemaleHospitalizationHumansIncidenceMaleMiddle AgedRiskRisk FactorsSampling StudiesSex DistributionTime Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11059439[21]. The stroke rate in those with lone AF, defined as younger than 60 without evidence of cardiopulmonary disease, remains at 1.3% per year ADDIN EN.CITE Kopecky19872503627174317111987Sep 10The natural history of lone atrial fibrillation. A population-based study over three decades669-74Kopecky, S. L.Gersh, B. J.McGoon, M. D.Whisnant, J. P.Holmes, D. R., Jr.Ilstrup, D. M.Frye, R. L.N Engl J MedAdolescentAdultAgedAtrial Fibrillation/*complications/mortalityCerebrovascular Disorders/etiologyFemaleFollow-Up StudiesHumansMaleMiddle AgedMyocardial Infarction/etiologyPulmonary Embolism/etiologyRecurrencehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3627174[22]. Stroke rates can be reduced significantly with the use of oral anticoagulation and, to a lesser degree, with aspirin. A meta-analysis of sixteen trials, including Stroke Prevention in Atrial Fibrillation, revealed that adjusted-dose warfarin reduced stroke by 62% while ASA reduced stroke by only 22% ADDIN EN.CITE Hart19992601050795713171999Oct 5Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis492-501Department of Medicine (Neurology), University of Texas Health Science Center, San Antonio 78284, USA.Hart, R. G.Benavente, O.McBride, R.Pearce, L. A.Ann Intern MedAnticoagulants/adverse effects/*therapeutic useAspirin/adverse effects/*therapeutic useAtrial Fibrillation/*complicationsCerebrovascular Disorders/*prevention & controlHemorrhage/chemically inducedHumansPlacebosPlatelet Aggregation Inhibitors/*therapeutic useRandomized Controlled TrialsResearch Support, U.S. Gov't, P.H.S.Warfarin/adverse effects/*therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10507957[23]. Similar multi-trial analysis suggests that patients who are below 65 and without a history of transient ischemic attacks, diabetes mellitus and hypertension have a stroke risk of less than 1% per year without warfarin ADDIN EN.CITE 19942708018000154131994Jul 11Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials1449-57Arch Intern MedAgedAnalysis of VarianceAnticoagulants/*therapeutic useAspirin/therapeutic useAtrial Fibrillation/complications/*drug therapyCerebrovascular Disorders/etiology/*prevention & controlFemaleFibrinolytic Agents/*therapeutic useHumansMaleMiddle AgedRandomized Controlled TrialsResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Risk FactorsTreatment OutcomeWarfarin/therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8018000[24]. Based on these studies, it is strongly recommended that patients with AF be treated with warfarin at a goal INR 2-3. Aspirin alone may be acceptable in patients younger than 60 years who have no hypertension, diabetes or evidence of cardiovascular disease.
15. Is immediate cardioversion with TEE better than delayed cardioversion after anticoagulation?
Immediately after either electrical or pharmacological cardioversion, there is transient left atrial dysfunction known as stunning. Depending on how long the patient has been in AF, stunning can last for several weeks and predisposes patients to thromboembolism. Patients with evidence of a thrombus in the left atrial appendage seen on transesophageal echocardiogram are at a particularly high risk of thromboembolic events. The risk of an embolic event without anticoagulation has been reported to vary from 1-5% in patients with persistent AF, but is closer to 0.8% in those who have been in AF for less than 48 hours ADDIN EN.CITE Naccarelli2000290108220398510A2000May 25Cost-effective management of acute atrial fibrillation: role of rate control, spontaneous conversion, medical and direct current cardioversion, transesophageal echocardiography, and antiembolic therapy36D-45DDivision of Cardiology, Cardiovascular Center, Pennsylvania State University, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.Naccarelli, G. V.Dell'Orfano, J. T.Wolbrette, D. L.Patel, H. M.Luck, J. C.Am J CardiolAlgorithmsAmiodarone/therapeutic useAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/drug therapy/economics/surgery/*therapyAtrial Flutter/drug therapyCost-Benefit AnalysisEchocardiography, TransesophagealElectric CountershockFlecainide/therapeutic useHumansProcainamide/therapeutic usePropafenone/therapeutic useQuinidine/therapeutic useSotalol/therapeutic useVerapamil/therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10822039[25]. In a multicenter, randomized prospective trial, 1222 patients with AF of greater than 48 hours duration were either anticoagulated for 3 to 4 weeks before cardioversion or had earlier cardioversion guided by transesophageal echocardiography ADDIN EN.CITE Klein200130011346805344192001May 10Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation1411-20Cleveland Clinic Foundation, Department of Cardiology, OH 44195, USA. kleina@ccf.orgKlein, A. L.Grimm, R. A.Murray, R. D.Apperson-Hansen, C.Asinger, R. W.Black, I. W.Davidoff, R.Erbel, R.Halperin, J. L.Orsinelli, D. A.Porter, T. R.Stoddard, M. F.N Engl J MedAgedAnticoagulants/adverse effects/*therapeutic useAtrial Fibrillation/complications/*therapy/ultrasonographyCerebrovascular Accident/etiologyComparative Study*Echocardiography, Transesophageal*Electric Countershock/methodsEmbolism/etiologyFemaleHeart Atria/ultrasonographyHeart Diseases/drug therapy/*ultrasonographyHemorrhage/chemically inducedHeparin/adverse effects/therapeutic useHumansIschemic Attack, Transient/etiologyMaleMiddle AgedMortalityProspective StudiesResearch Support, Non-U.S. Gov'tThromboembolism/prevention & controlThrombosis/drug therapy/*ultrasonographyWarfarin/adverse effects/therapeutic usehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11346805[26]. There were no significant differences in rates of embolic events, however, the group guided by transesophageal echo had a greater rate of successful restoration of sinus rhythm and fewer hemorrhagic events. The decision of one approach over the other may be guided primarily by patient preference, but this study suggested that both approaches are equally effective in reducing stroke rates.
16. Do patients with paroxysmal atrial fibrillation need to be anticoagulated for life?
Anticoagulation can be burdensome because of the close monitoring that is necessary and bruising associated with the therapy. Many patients understandably request that anticoagulation be stopped, especially patients with paroxysmal AF who have not felt any symptoms over a long period of time. The stroke risk, however, is equivalent between patients with persistent and patients with chronic AF ADDIN EN.CITE Hart2000310106362783512000JanStroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators183-7Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA. HartR@uthscsa.eduHart, R. G.Pearce, L. A.Rothbart, R. M.McAnulty, J. H.Asinger, R. W.Halperin, J. L.J Am Coll CardiolAgedAnti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverseeffectsAspirin/*administration & dosage/adverse effectsAtrial Fibrillation/*complicationsCerebrovascular Accident/etiology/*prevention & controlCohort StudiesDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansLongitudinal StudiesMaleMiddle AgedRecurrenceResearch Support, U.S. Gov't, P.H.S.Risk FactorsWarfarin/administration & dosage/adverse effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10636278[27]. When patients were recorded with continuous electrocardiograms over a 28 day period, however, most patients with paroxysmal AF experienced asymptomatic episodes of AF ADDIN EN.CITE Page199432082816518911994JanAsymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia224-7Department of Medicine, Duke University Medical Center, Durham, NC.Page, R. L.Wilkinson, W. E.Clair, W. K.McCarthy, E. A.Pritchett, E. L.CirculationAtrial Fibrillation/*diagnosis/epidemiologyComparative StudyConfidence Intervals*Electrocardiography, Ambulatory/methodsFemaleHumansMaleMiddle AgedResearch Support, U.S. Gov't, P.H.S.Stochastic ProcessesTachycardia, Paroxysmal/*diagnosis/epidemiologyTachycardia, Supraventricular/*diagnosis/epidemiologyTime Factorshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8281651[28]. Patients will experience asymptomatic episodes even when they claim to know exactly when they are in the arrhythmia. There is no easy way to identify patients who will stay in sinus rhythm and no longer be at risk for thromboembolic events. Although it is not known definitively if asymptomatic episodes of AF are associated with increased risk of stroke, at this moment there is no evidence to suggest that stopping anticoagulation after maintenance of sinus rhythm is safe.
17. What should be the goal INR in patients with atrial fibrillation and is it safe to hold anticoagulation for surgery?
Anticoagulation is a balance between prevention of embolic strokes and avoidance of hemorrhagic events. Although major gastrointestinal bleeding can be life-threatening, hemorrhagic strokes can be equally devastating. In patients being anticoagulated for AF, it is important to minimize the risk of over-anticoagulation with careful monitoring of INR. The risk of stroke rises significantly when the INR is below 2.0 and the risk of intracranial bleeding begins to rise above an INR of 3.0 ADDIN EN.CITE Hylek1996330867893133581996Aug 22An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation540-6Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.Hylek, E. M.Skates, S. J.Sheehan, M. A.Singer, D. E.N Engl J MedAdultAgedAnticoagulants/*administration & dosage/adverse effectsAtrial Fibrillation/complications/*drug therapyBrain Ischemia/etiology/*prevention & controlCase-Control StudiesCerebrovascular Disorders/etiology/prevention & controlDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedOdds RatioResearch Support, Non-U.S. Gov'tRisk FactorsWarfarin/*administration & dosage/adverse effectshttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8678931[29]. It is therefore recommended that patients be kept on warfarin with a goal INR between these two values. With the understanding that the 1-5% stroke risk is estimated over the course of a year, it was deemed safe by the joint committee to recommend that in patients undergoing surgery or other invasive procedures, it is acceptable to hold anticoagulation for up to one week without the use of heparin ADDIN EN.CITE Fuster20011011673357104172001Oct 23ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology2118-50Fuster, V.Ryden, L. E.Asinger, R. W.Cannom, D. S.Crijns, H. J.Frye, R. L.Halperin, J. L.Kay, G. N.Klein, W. W.Levy, S.McNamara, R. L.Prystowsky, E. N.Wann, L. S.Wyse, D. G.Gibbons, R. J.Antman, E. M.Alpert, J. S.Faxon, D. P.Gregoratos, G.Hiratzka, L. F.Jacobs, A. K.Russell, R. O.Smith, S. C., Jr.Alonso-Garcia, A.Blomstrom-Lundqvist, C.de Backer, G.Flather, M.Hradec, J.Oto, A.Parkhomenko, A.Silber, S.Torbicki, A.CirculationAgedAged, 80 and overAlgorithmsAnti-Arrhythmia Agents/therapeutic useAtrial Fibrillation/classification/*diagnosis/epidemiology/*therapyAtrial Flutter/diagnosisComorbidityContinental Population GroupsDiagnosis, DifferentialDisease ManagementElectric CountershockElectrocardiographyFemaleFibrinolytic Agents/therapeutic useHumansMaleMiddle AgedPrevalencePrognosisRisk AssessmentTachycardia/diagnosisThromboembolism/etiology/prevention & controlhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11673357[1]. If interruption of warfarin is necessary for a period longer than one week, it has been recommended that either intravenous unfractionated heparin or subcutaneous low molecular weight heparin be administered.
18. What can be done when patients do not respond adequately to medical therapy?
Most patients with atrial fibrillation will be adequately managed with anticoagulation and rate control. Patients who have symptomatic AF or can not be adequately rate controlled are often exposed to numerous antiarrhythmic agents. There is a group of patients, however, who remain symptomatic despite antiarrhythmic therapy or who can not tolerate these agents due to side effects. These are the patients who often seek non-pharmacologic approaches to the prevention of recurrent AF. There are multiple approaches that have been studied in this setting, including surgical incision of the atrium, atrial pacing and implantable atrial defibrillators. An emerging therapy is catheter based ablation. After the discovery that ectopic stimuli from the veins can induce AF ADDIN EN.CITE Haissaguerre19983409725923339101998Sep 3Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins659-66Hopital Cardiologique du Haut-Leveque, Bordeaux-Pessac, France.Haissaguerre, M.Jais, P.Shah, D. C.Takahashi, A.Hocini, M.Quiniou, G.Garrigue, S.Le Mouroux, A.Le Metayer, P.Clementy, J.N Engl J MedAdolescentAdultAgedAtrial Fibrillation/*etiology/surgeryAtrial PrematureComplexes/*complications/diagnosis/physiopathology/surgery*Catheter AblationElectrocardiographyFemaleHumansMaleMiddle AgedPulmonary Veins/*physiopathology/surgeryRecurrenceTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9725923[30], techniques to electrically isolate the pulmonary veins from the atrium have been developed. In one study of 251 patients who underwent pulmonary vein isolation, after 10 months, 85% of patients with paroxysmal and 68% of patients with permanent AF maintained sinus rhythm based on serial Holter monitoring ADDIN EN.CITE Pappone200135011714647104212001Nov 20Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation2539-44Department of Cardiology, San Raffaele University Hospital, Milan, Italy. carlo.pappone@hsr.itPappone, C.Oreto, G.Rosanio, S.Vicedomini, G.Tocchi, M.Gugliotta, F.Salvati, A.Dicandia, C.Calabro, M. P.Mazzone, P.Ficarra, E.Di Gioia, C.Gulletta, S.Nardi, S.Santinelli, V.Benussi, S.Alfieri, O.CirculationAtrial Fibrillation/pathology/physiopathology/*surgeryCatheter Ablation/adverse effects/*methodsCohort StudiesElectrophysiologic Techniques, CardiacFeasibility StudiesHeart Atria/pathology/physiopathologyHeart RateHumansMiddle AgedPulmonary Veins/*surgeryTreatment Outcomehttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11714647[31]. The major risk of this procedure is pulmonary vein stenosis and cardiac tamponade which was observed in 0.8% of patients in this study.
19. When is atrioventricular node (AVN) ablation necessary?
Many untreated patients with AF can mount ventricular response rates to 170 beats per minute. The major disadvantage of these rapid rates is that most patients become symptomatic and can, over time, develop tachycardia-mediated cardiomyopathy. Based on the AFFIRM trial, a reasonable goal in the rate control strategy is a heart rate below 80 at rest and below 110 during a six minute walk test ADDIN EN.CITE Wyse20027012466506347232002Dec 5A comparison of rate control and rhythm control in patients with atrial fibrillation1825-33AFFIRM Clinical Trial Center, Axio Research, 2601 4th Ave., Ste. 200, Seattle, WA 98121, USA.Wyse, D. G.Waldo, A. L.DiMarco, J. P.Domanski, M. J.Rosenberg, Y.Schron, E. B.Kellen, J. C.Greene, H. L.Mickel, M. C.Dalquist, J. E.Corley, S. D.N Engl J MedAdrenergic beta-Antagonists/therapeutic useAgedAmiodarone/therapeutic useAnti-Arrhythmia Agents/adverse effects/*therapeutic useAtrial Fibrillation/complications/mortality/*therapyCalcium Channel Blockers/therapeutic useCatheter AblationCerebrovascular Accident/etiologyCombined Modality TherapyComparative StudyCross-Over Studies*Electric CountershockFemaleHeart RateHumansMaleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.Survival Analysishttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12466506[6]. In patients who can not achieve rate control, become excessively bradycardic or are symptomatic with medical therapy, AV nodal ablation followed by pacemaker implantation is an option. In the AIRCRAFT trial, 99 highly symptomatic patients with persistent AF were randomized to AVN ablation plus pacemaker versus aggressive pharmacologic approach ADDIN EN.CITE Weerasooriya20033601276764941102003May 21The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial (AIRCRAFT)1697-702Department of Cardiology, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia. rukshen@hotmail.comWeerasooriya, R.Davis, M.Powell, A.Szili-Torok, T.Shah, C.Whalley, D.Kanagaratnam, L.Heddle, W.Leitch, J.Perks, A.Ferguson, L.Bulsara, M.J Am Coll CardiolActivities of Daily LivingAgedAnti-Arrhythmia Agents/adverse effects/therapeutic useAtrial Fibrillation/physiopathology/*therapyAtrioventricular Node/surgeryCatheter Ablation/adverse effectsComparative StudyEchocardiographyElectrocardiography, AmbulatoryExercise TestFemaleHumansMalePacemaker, Artificial/adverse effectsQuality of LifeResearch Support, Non-U.S. Gov'tStroke VolumeVentricular Function, Lefthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12767649[32]. The patients randomized to the AVN ablation plus pacemaker approach were less symptomatic at one year. Although an increasing number of patients with AF refractory to medical therapy will undergo ablation for pulmonary vein isolation (PVI), the AVN ablation plus pacemaker approach may be reserved for those with sick sinus syndromes or those who fail PVI.
20. Are there genetic tests for patients with lone atrial fibrillation?
The genetics of atrial fibrillation is an emerging field. Thus far only two genes, including KCNQ1 which encodes a potassium channel, have been identified as the cause of lone atrial fibrillation in certain families ADDIN EN.CITE Chen20033701252225129956042003Jan 10KCNQ1 gain-of-function mutation in familial atrial fibrillation251-4Department of Cardiology, Tongji Hospital, and Institute of Medical Genetics, Tongji University, 399 Xin Cun Road, Shanghai 200065, People's Republic of China. drchen@public7.sta.net.cnChen, Y. H.Xu, S. J.Bendahhou, S.Wang, X. L.Wang, Y.Xu, W. Y.Jin, H. W.Sun, H.Su, X. Y.Zhuang, Q. N.Yang, Y. Q.Li, Y. B.Liu, Y.Xu, H. J.Li, X. F.Ma, N.Mou, C. P.Chen, Z.Barhanin, J.Huang, W.ScienceAction PotentialsAdolescentAdultAgedAnimalsAtrial Fibrillation/*genetics/physiopathologyCOS CellsChildChinaChromosomes, Human, Pair 11/geneticsElectrocardiographyFemaleHaplotypesHeart Atria/physiopathologyHeart Ventricles/physiopathologyHumansLod ScoreLong QT Syndrome/genetics/physiopathologyMaleMicrosatellite RepeatsMiddle AgedMutation*Mutation, MissenseMyocytes, Cardiac/*physiologyPatch-Clamp TechniquesPedigreePotassium Channels/*genetics/physiology*Potassium Channels, Voltage-GatedResearch Support, Non-U.S. Gov'thttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12522251[33]. There are probably multiple, yet unidentified genes that cause lone atrial fibrillation in other families. AF that is acquired later in life, on the other hand, is likely multifactorial and is probably due to a combination of different susceptibility genes and exposures to environmental factors. The genetic studies are essential in helping us understand the pathophysiology of atrial fibrillation, which although is the most common arrhythmia in adults, is the least well understood. At the moment, genetic testing in patients with AF is not routinely recommended. As more genes are discovered in the future, especially in families with lone atrial fibrillation, it may become routine to perform genetic tests and treat prophylactically for the prevention of development of AF.
QUOTE EN.REFLIST 1. Fuster, V., et al., ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology. Circulation, 2001. 104(17): p. 2118-50.
2. Benjamin, E.J., et al., Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. Jama, 1994. 271(11): p. 840-4.
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6. Wyse, D.G., et al., A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med, 2002. 347(23): p. 1825-33.
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10. Falk, R.H., et al., Digoxin for converting recent-onset atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. Ann Intern Med, 1987. 106(4): p. 503-6.
11. Page, R.L., et al., Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. J Am Coll Cardiol, 2002. 39(12): p. 1956-63.
12. Roden, D.M., Risks and benefits of antiarrhythmic therapy. N Engl J Med, 1994. 331(12): p. 785-91.
13. Botto, G.L., et al., External cardioversion of atrial fibrillation: role of paddle position on technical efficacy and energy requirements. Heart, 1999. 82(6): p. 726-30.
14. Miller, M.R., et al., Efficacy of agents for pharmacologic conversion of atrial fibrillation and subsequent maintenance of sinus rhythm: a meta-analysis of clinical trials. J Fam Pract, 2000. 49(11): p. 1033-46.
15. Tieleman, R.G., et al., Efficacy, safety, and determinants of conversion of atrial fibrillation and flutter with oral amiodarone. Am J Cardiol, 1997. 79(1): p. 53-7.
16. Maisel, W.H., et al., Risk of initiating antiarrhythmic drug therapy for atrial fibrillation in patients admitted to a university hospital. Ann Intern Med, 1997. 127(4): p. 281-4.
17. Freeland, S., C. Worthy, and M. Zolnierz, Initiation and monitoring of class III antiarrhythmic agents. J Cardiovasc Electrophysiol, 2003. 14(12 Suppl): p. S291-5.
18. Alboni, P., et al., Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach. N Engl J Med, 2004. 351(23): p. 2384-91.
19. Madrid, A.H., et al., Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation, 2002. 106(3): p. 331-6.
20. Healey, J.S., et al., Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol, 2005. 45(11): p. 1832-9.
21. Frost, L., et al., Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation. Am J Med, 2000. 108(1): p. 36-40.
22. Kopecky, S.L., et al., The natural history of lone atrial fibrillation. A population-based study over three decades. N Engl J Med, 1987. 317(11): p. 669-74.
23. Hart, R.G., et al., Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med, 1999. 131(7): p. 492-501.
24. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med, 1994. 154(13): p. 1449-57.
25. Naccarelli, G.V., et al., Cost-effective management of acute atrial fibrillation: role of rate control, spontaneous conversion, medical and direct current cardioversion, transesophageal echocardiography, and antiembolic therapy. Am J Cardiol, 2000. 85(10A): p. 36D-45D.
26. Klein, A.L., et al., Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med, 2001. 344(19): p. 1411-20.
27. Hart, R.G., et al., Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol, 2000. 35(1): p. 183-7.
28. Page, R.L., et al., Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia. Circulation, 1994. 89(1): p. 224-7.
29. Hylek, E.M., et al., An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med, 1996. 335(8): p. 540-6.
30. Haissaguerre, M., et al., Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med, 1998. 339(10): p. 659-66.
31. Pappone, C., et al., Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation, 2001. 104(21): p. 2539-44.
32. Weerasooriya, R., et al., The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial (AIRCRAFT). J Am Coll Cardiol, 2003. 41(10): p. 1697-702.
33. Chen, Y.H., et al., KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science, 2003. 299(5604): p. 251-4.
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