Atrial fibrillation (AF) care pathways. for the primary care physicians

Atrial fibrillation (AF) care pathways for the primary care physicians by University of Minnesota Physicians Heart, October, 2011 Evaluation by the primary care physician: 1. Comprehensive history and physical examination. Some apparent causes such as binge drinking ( holiday heart syndrome ), stimulant abuse, febrile diseases and hyperthyroidism may be easily diagnosed and managed without the need of long-term cardiac drug therapy. Hypertension and other apparent structural heart diseases are frequently associated with AF but may or may not be the direct cause of AF. Most importantly, while the majority of the underlying causative conditions are not curable, they may be substantially ameliorated by proper care and thereby reduce arrhythmia susceptibility. 2. CBC with differential is helpful, particularly when anticoagulation is considered. The baseline level of hemoglobin can serve as a useful reference for monitoring bleeding/anemia. 3. BMP (basic metabolic panel) results can be helpful for the selection or dosage determination of some rhythm-control drugs. For example, patients with renal insufficiency may not be good candidates for sotalol or dofetilide. If considered beneficial, a lower dose may be recommended. 4. TSH is a useful screening test to exclude hyperthyroidism as the cause of AF. In patients with known hypothyroidism, TSH measurement can exclude iatrogenic hyperthyroidism as a result of over-treatment. TSH should also be followed if patient is being treated with amiodarone. 5. 12-lead ECG is the gold standard for establishing the diagnosis of AF. It is understood that a 12-lead ECG may miss AF in patients with paroxysmal AF and a Holter monitor or ECG event monitor may be needed to confirm the diagnosis. Cardiology consultation is recommended for all patients with newly diagnosed AF or palpitations that may be due to as yet unconfirmed AF because the management strategy may vary widely according to individual patient conditions. However, not all patients with AF need long-term routine cardiology/electrophysiology follow-up. Patients with the initial episode of

spontaneously converted AF, or selected patients with persistent AF with well controlled ventricular rate and no symptoms can be managed by primary care physicians. The latter advice is not, however, applicable in young (<55 years) patients in whom AF is not typically expected, or individuals with suspected underlying structural heart disease (e.g. prior MI, valvular disease, cardiomyopathy), or in the setting of Pre-excitation syndrome (Wolff- Parkinson-White [WPW] syndrome) or long QT syndrome. The following tests may be helpful in risk stratifying patients, and can be requested by the attending physician or at a later stage by the cardiologist 1. Echocardiograhy is helpful to guide patient management and is recommended for almost all AF patients. Left ventricular ejection fraction and left atrial diameter are the essential parameters in making therapeutic decisions, particularly for selection of the rate- or rhythm-control drugs, and anticoagulation. 2. Holter monitoring is most frequently used in patients with persistent AF to assess the appropriateness of rate control in patients with persistent AF. However, it is understood that AF patients tend to have extreme ventricular rate responses, with very rapid heart rate during minor exertion and severe bradycardia at rest or during sleep. Thus, there is not a well-accepted criterion of optimal average, minimal or maximal ventricular rate. Further research in this area is needed. Holter monitoring is also used in selected patients with paroxysmal AF to assess the ventricular rate during AF (for tachycardia) and sinus rhythm (for bradycardia). The following tests are most often ordered by the cardiologists/electrophysiologists to whom patients are referred: 3. Ambulatory ECG event monitoring (AECG, including mobile cardiac outpatient telemetry, MCOT) is useful for detection of paroxysmal AF (either symptomatic or asymptomatic) or severe bradycardia. AECG can also be used to assess the ventricular rate during symptoms in patients with persistent AF. In addition, it may be used for monitoring proarrhythmic side effects in patients taking antiarrhythmic drugs. 4. Exercise stress test, or stress echocardiography is generally not necessary for evaluation of AF but may be considered if AF is mostly exercise-triggered or symptoms of myocardial ischemia are present. In selected patients with persistent AF, exercise stress test can be used to assess the ventricular rate during exercise. 5. Nuclear cardiac scan generally is not necessary for evaluation of AF and is considered only if myocardial ischemia is strongly suspected.

6. Cardiac CT and MRI are generally not recommended for initial evaluation of AF. They are used to define the cardiac anatomy (left atrium and pulmonary veins) before catheter ablation of AF. They are also used to assess the cardiac (including coronary artery) anatomy and myocardium if there are other indications for these tests. 7. Coronary angiography is usually not a part of AF evaluation and is only considered based on other standard indications. 8. Electrophysiology study is recommended if a primary etiology of AF (such as the Wolff- Parkinson-White syndrome or focal atrial tachycardia) is suspected and an ablation procedure is planned. It is also an integral part of the catheter ablation procedure for AF. Treatment: 1. To treat or not to treat? Not all patients with AF need long-term drug therapy. a. Patients with clear reversible etiology of AF only need correction of the underlying etiology (e.g., hyperthyroidism, acute alcohol abuse). b. Because of the often life-time commitment, patients with the initial episode of spontaneously converted AF of unknown etiology can be followed without rateor rhythm-control drug therapy after comprehensive cardiac evaluation. Similar recommendation can be made for selected patients with the initial episode of persistent AF that require pharmacological or electrical cardioversion if the risk of AF recurrence is predicted to be low. The above approach may be particularly beneficial in otherwise young and healthy individuals. Exceptions are patients who have asymptomatic AF with one or more of the following: rapid ventricular rate (resting average heart rate>110 beats/minute), patients whose first presentation is stroke or tachycardia-induced cardiomyopathy. 2. Anticoagulation: Not all patients with AF need long-term anticoagulation. Indications for anticoagulation in non-valvular AF patients are based on the CHADS2 score in the US and CHA2DS2-Vasc score in some European countries. AF patients with established diagnosis of rheumatic valvular disease or those with mechanical heart valves require long-term oral anticoagulation. A. Risk Stratification CHADS2 stands for Congestive heart failure (score =1), Hypertension (score=1), Age >75 years (score=1), Diabetes (score=1) and Stroke/TIA (score=2). A total score of 2 mandates anticoagulation unless there is a contraindication. A total

score of 1 may be treated either with aspirin or a standard oral anticoagulant. The final decision is based on patient preference, difficulty of INR titration, and physician-perceived risk of potential stroke and bleeding. A total score of 0 has no indication for a standard oral anticoagulant. Anticoagulation in this group of AF patients is considered a class III indication (no benefit or harmful). CHA2DS2-Vasc (New European criteria for anticoagulation) stands for Congestive heart failure (score= 1), Hypertension (score= 1), Age (>65 score=1, >75 score=2), Diabetes (score=1), Stroke/TIA (score=2), Female (score=1), Arterial disease (history of MI, peripheral arterial disease or aortic plaque, score=1). A total score of 2 indicates for a standard oral anticoagulant. The CHA2DS2-Vasc score is not yet listed in the US guidelines for anticoagulation but may help a physician to make recommendation in patients with a total CHADS2 score of 1. B. Contraindications for anticoagulation: It should be understood that previous randomized trials of anticoagulation in patients with AF excluded patients at risk of bleeding. The following conditions are considered contraindications for anticoagulation: alcoholism, liver dysfunction, history of intracranial bleeding, untreated GI or urinary tract bleeding, recurrent falls, hereditary or acquired bleeding disorders, and non-compliance. C. Anticoagulant Drugs Warfarin (Coumadin, Jantoven ), a vitamin K antagonist, is the most commonly used oral anticoagulant. Its major advantage is the relatively low cost because of the availability of generic formulas. Its major disadvantage is the requirement for routine INR monitoring. A therapeutic INR of 2-3 can be consistently achieved in only about 60-70% of patients, even with good compliance. Other coumarin derivatives are occasionally seen in patients travelling from other countries. Dabigartran (Pradaxa) is a new oral anticoagulant that was approved by FDA after a head to head comparison trial with warfarin in 18,113 patients. As a direct thrombin inhibitor, it does not need INR monitoring. Its current major disadvantage is high cost (cash pay of about $250/month) and tier III coverage or preauthorization requirement by some insurance companies. In addition, dabigatran has a relatively high incidence (about 20%) of GI adverse reaction. In comparison with warfarin, dabigartran 150 mg bid was more effective for stroke prevention (annual stroke rate 1.69% vs 1.1%, p<0.001) and has a lower rate of intracranial bleeding (annual incidence 0.38% vs 0.1%, p<0.001). The standard dose of dabigatran is 150 mg po bid. The 75 mg bid dose is only approved for patients with creatinine clearance of 15-30 ml/minute. Dosing

recommendation for patients with creatinine <15 ml/minute or hemodialysis cannot be provided. Two new agents (apxiaban and rivaroxaban), both factor Xa inhibitors, have been tested in large randomized trials and are shown to be superior to warfarin (with lower incidence of stroke and less risk of intracranial bleeding). These agents may be released to the market in the next couple of years. Aspirin has been studied extensively in randomized trials and was found to be inferior to warfarin for stroke prevention in AF patients. Aspirin is appropriate for AF patients who have CHADS2 score 0 or those who cannot take warfarin or dabigatran. D. Initiating anticoagulation Oral anticoagulants (warfarin or dabigartran) can be initiated by the primary care physician in the clinic, emergency room or hospital. The primary rationale for anticoagulation in AF patients is for long-term prevention of stroke/thromboembolism. Newly diagnosed AF patients with indication for long-term anticoagulation may not need intravenous heparin or subcutaneous low molecular weight heparin during initiation of oral anticoagulation. Exceptions are patients who present with embolic stroke, or patients with AF duration >48 hours and are scheduled for pharmacological or electrical cardioversion. For the remaining patients, bridging using intravenous heparin or subcutaneous low molecular weight heparin until therapeutic INR is not required. Reducing the unnecessary use of intravenous heparin or subcutaneous low molecular weight heparin will not only reduce cost but also improve patient satisfaction without sacrificing quality of care. E. Duration of anticoagulation Anticoagulation for 3-4 weeks is recommended if a patient with persistent AF is scheduled for elective DC cardioversion. For patients taking dabigatran, DC cardioversion can be performed 3-4 weeks later without INR measurement. For patients taking warfarin, many cardiologists require 4 consecutive weekly INR>2.0 before DC cardioversion. Such a requirement often creates delay (frequently repeat delay) of cardioversion because of the known difficulty in achieving therapeutic INR consistently. If an early cardioversion is desired, a practical alternative is to perform a TEE (transesophageal echocardiography) and proceed to DC cardioversion if TEE does not show a left atrial thrombus. The above recommendation does not apply to emergency DC cardioversion. AF patients with hypotension or pulmonary edema resulting from rapid ventricular rate

that cannot be managed with intravenous rate control drugs should receive emergency DC cardioversion as soon as possible. Anticoagulation can be initiated after the cardioversion and maintained for 1 month if the AF duration is >48 hours. In such cases, intravenous heparin or subcutaneous low molecular weight heparin may be used to overlap with warfarin until therapeutic INR is achieved. A more practical approach is to use dabigatran which can avoid the need for heparin. For patients with the AF duration >48 hours and CHADS2 score 0 who are scheduled for elective DC cardioversion, no clinical trial data on anticoagulation are available before cardioversion but anticoagulation for about 1 month after cardioversion is considered beneficial based on the theory of atrial stunning (reduced atrial contraction with potential risk of new clot formation post cardioversion). Majority of cardiologists may prefer full anticoagulation or TEE before cardioversion for patients with persistent AF >48 hours and CHADS2 score 0. In the absence of a contraindication, the duration of continued anticoagulation after cardioversion is at least 1 month (in the case of warfarin, with INRs documented to be >2.0 during that time) if there is no AF recurrence. For patients with CHADS2 score 2 and no AF recurrence, some experts have recommended continuation of anticoagulation indefinitely although there are no clinical trial data to support such recommendation. For patients with paroxysmal AF and CHADS2 score 2, if their AF is clinically controlled with an antiarrhythmic drug, it is reasonable to continue anticoagulation indefinitely. For patients who have catheter ablation of AF, anticoagulation is recommended for at least 3 months. Afterwards, anticoagulation may be discontinued if it is reasonably certain based on AECG monitoring that there is no AF recurrence and CHADS2 score is 1. Patients with successful catheter ablation of AF and CHADS2 score 2 may still need anticoagulation beyond 3 months after the ablation procedure. F. Peri-operative anticoagulation: AF patients on oral anticoagulation may withhold anticoagulation for <1 week or as short as required for safe performance of the surgical procedure. Such a recommendation may also apply to patients scheduled for coronary angiography or other interventional vascular procedures. Heparin bridging is recommended for patients with mechanical heart valves and may be beneficial in patients with recent stroke. G. Anticoagulation in patients undergoing EP procedures: Anticoagulation is usually withheld for 1-3 days before pacemaker implant or replacement, and AV node ablation except for patients with mechanical heart valves, recent (<6 months) stroke or pulmonary embolism.

Certain pacemaker implanting physicians no longer withhold warfarin anticoagulation if the INR is <3, and the plan should be discussed with the implanter. Continued anticoagulation is recommended if cardioversion, defibrillation testing (for ICD implantation or replacement) is expected during the procedure. Anticoagulation with therapeutic INR is recommended for patients scheduled for AF ablation. 3. Rate control: a. The selection of intravenous rate control medication depends on the physician preference/experience. The most commonly used agent is diltiazem. Intravenous esmolol has a short half-life and may be more appropriate for patients with acute myocardial infarction but may not be appropriate for patients with asthma. Intravenous digoxin may have mild to moderate rate control effect but it may take a couple of hours to see such an effect. The advantage of digoxin is absence of hypotension. Digoxin has no effect for AF conversion. Intravenous amiodarone may have mild to moderate rate control effect but has the potential side effect of hypotension. It is not cost-effective to use intravenous amiodarone for the sole purpose of rate control. b. Oral β-blockers are commonly used for long-term rate control. The choice of specific agent is dependent on physician preference. It is preferred for patients with heart failure or coronary artery disease and may not be appropriate for patients with asthma. It may have the side effects of fatigue and sexual dysfunction in some patients. c. Calcium channel blockers diltiazem and verapamil are also commonly used for rate control. It is preferred for patients with asthma and may have less negative impact on exercise tolerance. Its known side effects include leg edema and constipation but sexual dysfunction is rare. d. Digoxin has mild to moderate rate control effect but can be a useful combination with a β-blocker or calcium channel blocker for rate control. In addition, it may be useful in patients with heart failure. Overall, cardiac glycosides are no longer favored for rate control applications due to variable effectiveness. e. Oral amiodarone has certain rate control effect but are rarely used for the rate control purpose because of its cost and adverse side effect profile. Amiodarone has never been studied in a comparable manner and we cannot therefore comment on its safety when used for rate control in this setting.

f. AV node ablation is appropriate for patients who have AF with rapid ventricular rate that cannot be controlled with medications if maintenance of sinus rhythm is not feasible or not preferred. Because of complete AV block created intentionally pacemaker implantation is mandatory. AV node ablation is a practical approach to elderly patients with refractory AF with uncontrollable rapid ventricular rate. 4. Rhythm control: a. Initiation of rhythm-control antiarrhythmic drugs may be better left for the cardiologists. Maintenance of sinus rhythm is still preferred by many patients and pursued by many physicians. Equivalence of rhythm versus rate control reported in some clinical trials only apply to patients >65 years-old who had no preference about how their AF would be treated. In addition to limited efficacy, the benefit of maintaining sinus rhythm with the current antiarrhythmic drugs is counter-balanced by side effects. It should be understood that class II (βblockers) and IV (calcium channel blockers) antiarrhythmic drugs usually have no apparent effect for AF conversion or maintenance of sinus rhythm in most patients. β-blockers may have certain AF prevention effect in some CABG patients perioperatively. A β-blocker may also prevent recurrence in rare cases of focal AF. b. There has been a wide-spread use of intravenous amiodarone for emergency management of AF, an off label use. It should be understood that intravenous amiodarone has a very low rate of acute conversion of AF but does have certain rate-control effect, with the potential side effect of hypotension. c. Intravenous ibutilide (Corvert ) may be quite effective for acute conversion of new onset AF with duration <72 hours. It is better to avoid this drug in patients with acute heart failure, hypokalemia or hypomagnesemia, or baseline QTc interval >460 ms because those conditions pose increased risk of torsades de pointes. d. Elective DC cardioversion is highly successful to convert AF, with excellent safety when performed by an experienced medical team. However, maintenance of sinus rhythm usually requires the use of an antiarrhythmic drug. DC cardioversion without an antiarrhythmic drug is acceptable for initial episode of AF, or recurrent AF that happens more than 1 year apart. Emergency DC cardioversion is used for patients who are hemodynamically unstable because of AF. Urgent DC cardioversion in the emergency room may be cost-effective for

patients whose AF duration is clearly <48 hours and has no other ongoing major medical problems. e. Oral class Ia antiarrhythmic drugs quinidine, procainamide and disopyramide are not commonly used for AF in the contemporary practice because of side effects. Class Ic antiarrhythmic drugs flecainide and propafenone are recommended for patients without apparent structural heart disease. The QRS duration should be monitored with 12-lead ECG periodically and should not be 25% wider than the baseline. Some physicians may also prefer a treadmill test to further assess the QRS width during exercise. The concern for increased mortality associated with flecainide in patients with myocardial infarction and left ventricular dysfunction does not apply to AF patients without apparent structural heart disease. f. Oral class III antiarrhythmic drugs include amiodarone, dranedarone (Multaq), sotalol (Betapce ), and dofetilide (Tikosyn ). Amiodarone is the most effective agent for maintenance of sinus rhythm but its multiple long-term side effects have greatly limited its widespread use. Dranedarone (Multaq ) is not recommended in patients with ongoing or recent heart failure. There is a black box warning of liver failure required by FDA. Sotalol is appropriate for patients with coronary artery disease and should be used with caution in patients with severe left ventricular dysfunction (ejection fraction <35%) or diminished renal function. Dofetilide is appropriate for patients with coronary artery disease and left ventricular dysfunction/heart failure but requires admission to hospital for 3 days to initiate therapy. For both sotalol and dofetilide, the QT/QTc intervals should always be carefully monitored because of their potential risk of causing polymorphic ventricular tachycardia (torsades de pointes) and sudden death. The risk of torsades de pointes is more of a concern in female patients (who tend to have longer QT intervals than do males) and those taking diurectics (because of hypokalemia). g. Catheter ablation of AF has provided an opportunity of successful control for certain AF patients, particularly those with paroxysmal AF in the absence of structural heart disease. Many patients receive years of diminished arrhythmia symptoms with this procedure. The safety of stopping anticoagulation after an apparently successful ablation remains controversial, and this unknown should be discussed with prospective patients by the cardiologist/electrophysiologist. AF ablation may be recommended for AF patients who have apparent symptoms resulting from AF and failed 1 antiarrhythmic drugs. It is also occasionally

performed in young patients who decline life-time use of antiarrhythmic drugs. Before AF ablation, the patient should be informed about the alternative of rate control therapy using medications or AV node ablation plus pacemaker implantation. The current approach to AF ablation of the paroxysmal and persistent types is electrical isolation of the pulmonary veins, with or without left atrial linear ablation. Permanent AF is less often a candidate for ablation due to the procedure being more complex and the results less favorable. Most operators prefer using general anesthesia, mainly for the concern of ablation-induced pain. With operator experiences, the procedure duration has been shortened to about 3-4 hours and the major complication rate has been reduced to about <2%. Recurrent atrial tachyarrhythmia has been a major challenge, particularly within the first 3 month of the procedure. About half of those recurrent arrhythmias will resolve spontaneously over time. At the present time, a generally accepted single procedure success rate at 2 years is about 60-70% for paroxysmal AF and 40-50% for persistent AF. It should be understood that a comparison of efficacy between antiarrhythmic drug therapy (arrhythmia control) and catheter ablation (arrhythmia elimination) may not be fair. Furthermore, antiarrhythmic drug therapy and catheter ablation for AF are complimentary, not competitive therapies. 5. Care pathways: a. Elective cardiology consultation is appropriate: i. Patients with confirmed or suspected AF, in sinus rhythm during the office visit ii. Patients in AF, no symptoms and resting heart rate <110 beats/minute. iii. Patients in AF, with the only symptom of palpitation or fatigue. b. Hospital admission is appropriate: i. Selected patients in need of antiarrhythmic drug initiation (mostly dofetilide and sotalol). ii. Patients in AF, with shortness of breath or chest pain at rest iii. Patients in AF, with resting heart rate 110-150 beats/minute and worsening symptoms

c. ER visit is appropriate: i. Patients in AF, with resting heart rate >150 beats/minute ii. Patients in AF, with syncope or near syncope References: 1. 2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation. Fuster V et al. J Am Coll Cardiol, 2011; 57:101-198. 2. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).Wann L et al. J Am Coll Cardiol, 2011; 57:1330-1337.