Artrial fibrillation classification & management guideline

newer guidelines for management of atrial fibrillation.

1. Atrial Fibrillation Classification & Management guideline Dr. Rohan Sonawane JR MD (Internal medicine) Dr. V. P. Sinha MD, DM (Cardiology)

2. 1) Introduction 2) Classification 3) Mechanism of AF 4) Causes & Clinical Features 5) Diagnostic Evaluation 6) Management Guidelines

3. INTRODUCTION - Atrial fibrillation (AF) is a supraventricular arrhythmia which is disorganised, rapid & uncoordinated atrial activation characterized electrocardiographically by low-amplitude baseline oscillations ( fibrillatory or f waves) and an irregularly irregular ventricular rhythm. - The f waves have a rate of 300 to 600 beats/min and are variable in amplitude, shape, and timing. - The Ventricular rate during AF typically is100 – 160/min which can exceed > 250 beats/min in Wolf-Parkinson-White Syndrome due to conduction over accessory pathway.

4. Comparison between f waves of AF(top panel) and flutter waves of atrial flutter(bottom panel). Here f waves are variable in rate ,shape and amplitude whereas flutter waves are constant in rate and all aspects of morphology

5. AF with prominent f waves in V₁ that mimic atrial flutter waves. But the typical f waves are present in leads II and V₅, which establish the diagnosis of AF

6. A 12-lead ECG of AF in which f waves are not discernible. The irregularly irregular ventricular rate indicates that this is AF and not a junctional rhythm.

7. classification

8. TERM DEFINATION Paroxysmal AF - AF that terminates spontaneously or with intervention within 7 days of onset. (most < 24 hours) · Episodes may recur with variable frequency. Persistent AF -Continuous AF that is sustained >7 days. Longstanding persistent AF - Continuous AF of >12 months duration. Permanent AF -Continuous AF >12 months refractory to cardioverson -Permanent AF is used when there has been a joint decision by the patient and clinician to cease further attempts to restore and/or maintain sinus rhythm. Nonvalvular AF AF in the absence of rheumatic mitral stenosis , a mechanical or bioprosthetic heart valve, or mitral valve repair. Lone AF Individuals under 60 years old without clinical or echocardiographic evidence of cardiopulmonary disease,including hypertension These patients have a favorable prognosis with respect to thromboembolism and mortality.

9. -25% of paroxysmal AF -Initiated in setting of high vagol tone typically in evening when pt is relaxing or during sleep 10 - 15% of paroxysmal AF - in setting of high sympathetic tone like strenuous exercise

10. Mechanism of artial fibrillation Various phenotypes of AF have different electro physiologic characteristics because of remodelling and different clinical modulators that affect the substrate, such as heart failure, atrial stretch and ischemia, sympatho-vagal influences, inflammation and fibrosis. Electrophysiological mechanism: -- One or more automatic, triggered or micro-re entrant foci, so called drivers, which fires at rapid rates and cause fibrillation. Rapid discharges from pulmonary veins are the most common triggers of AF more so in Paroxysmal AF than in Persistent AF -- Multiple re-entrant circuits wondering throughout the artia , destroying and reforming wavelets that cause fibrillation. -- Other mechanism that seen in Persistent is change in atrial substrate, including interstitial fibrosis that causes slow, discontinuous and anisotropic conduction, may give rise to Complex Fractionated Atrial Electro gram ( CFAEs ) and re-entry

11. Causes & Clinical Features Causes of AF: Hypertension Ischemic heart disease Mitral valve disease Hypertrophic Cardiomyopathy Less common causes like restrictive cardiomyopathies like amyloidosis , constrictive pericarditis , Cardiac tumours and sever pulmonary hypertension, Thoracic or cardiac surgery. Wolf- Parkinson-White syndrome may degenerate in to AF Obesity- Atrial dilatation and increased systemic inflammatory factors like CRP are responsible for AF Obstructive sleep apnoea- Hypoxia, surge in autonomic tone and Hypertension are responsible for AF Temporary or reversible causes like Alcohol intake called “Holiday heart”. Most common correctible cause is hyperthyroidism.

12. Clinical Features: AF has a wide range of symptoms from none to severe disabling symptoms. The most common symptoms of AF are - Palpitation - Fatigue - Dypsnea - Effort intolerance - Light-headedness - Syncope- is an uncommon symptoms, most often caused by long sinus pause of AF in a patient with sick sinus syndrome or Drop in blood pressure due to sudden reduction in cardiac output in structurally heart diseases. - Some time asymptomatic patient does not seek medical care and directly present with stroke or heart failure.

13. Diagnostic Evaluation

14. Management of af Management of AF depends on Patient present in emergency with AF with rapid ventricular rate or patient haemodynamically stable or unstable, but overall Management of patients with AF involves 3, not mutually exclusive, objectives—rate control, prevention of thromboembolism and correction of the rhythm disturbance. Regardless of whether the rate control or rhythm control strategy is pursued, attention must also be directed to antithrombotic therapy for prevention of thromboembolism .

15. Rate control versus rhythm control The AFFIRM study and RACE trial have convincingly demonstrated that rate control is no inferior to rhythm control especially in asymptomatic or minimally symptomatic patients of age> 65yrs Decision of a rate control strategy v/s a rhythm control strategy is to be individualized taking several factors into account which include: Nature Frequency Severity of symptoms Length of time of AF Left atrial size (>5.0 cm) Other co morbidities Response to prior cardioversion Age Side effects and efficacy of drugs used Patient’s preference

16. Rate control An excessively rapid ventricular rate during AF results in uncomfortable symptoms and decrease effect intolerance and can cause a tachycardia induced cardiomyopathy if it is sustained for several weeks to month. Heart rate control must be assessed both at rest and during exertion. The goals of rate control according to AHA/ACC recommendations are as follows to achieve our desired heart rates: At rest :- 60-80 beats/min Mild to moderate exertion :- 90-115 beats/min During strenuous exercise :- 120-160 beats/min But recent randomized control trials have given 2 ways of rate control targets and comparative analysis of both of them : Lenient rate control Target was focused on getting the heart rate at < 110 beats /min Strict rate control Target was same as discussed above i.e. < 80 beats/min at rest and <110 beats/min with moderate exercise And finally it was found that lenient rate control was easier to achieve and was no inferior to strict rate control along with lesser mortality.

17. INTRAVENOUS AND ORAL RATE CONTROL AGENTS USED IN ATRIAL FIBRILLATION DRUGS INTRAVENOUS ADMINISTRATION ORAL ADMINISTRATION BETA BLOCKER: Metoprolol tartrate 2.5–5.0 mg IV bolus over 2 min; up to 3 doses 25–100 mg BID Metoprolol XL ( succinate ) N/A 50–400 mg QD Atenolol N/A 25–100 mg QD Esmolol 500 mcg/kg IV bolus over 1 min, then 50–300 mcg/kg/min IV N/A Propranolol 1 mg IV over 1 min, up to 3 doses at 2 min intervals 10–40 mg TID or QID Nodalol N/A 10-240 mg QD Carvedilol N/A 3.125- 25 mg BID Bisoprolol N/A 2.5 – 10 mg QD

18. Nondihydropyridine calcium channel antagonists: Verapamil (0.075-0.15 mg/kg) IV bolus over 2 min, may give an additional 10.0 mg after 30 min if no response, then 0.005 mg/kg/min infusion 180 – 480 mg QD (ER) Diltiazem 0.25 mg/kg IV bolus over 2 min, then 5-15 mg/h 120 – 360 mg QD (ER) Digitalis Glycosides : Digoxin 0.25 mg IV bolus repeat dosing to a maximum of 1.5 mg over 24 hours 0.125 – 0.25 mg QD Others : Amiodarone 300 mg IV over 1 hour, then 10 – 15 mg/h over 24 hours 100-200 mg QD

19. Rhythm control In patient with persistent AF it is reasonable to attempt to restore sinus rhythm at least in once in patients <65 yr old or in patients > 65 years old who are symptomatic from AF despite heart rate control. If the AF has been continuous for more than 1 year or if the left atrial diameter is very large ( > 5 cm), there is high probability of an early recurrence. It all depends on the attending clinician about the method of rhythm control to be applied to the patient which are: DC cardiversion Pharmacological cardioversion Hybrid therapy

20. Hybrid therapy is one in which early rhythm control is achieved by electrical cardioversion and concurrently after that patient is put on antiarrhythmic drugs to maintain sinus rhythm Treatment by cardioversion without daily antiarrhythmic drug therapy is appropriate if episodes of AF are separated by at least 6 months. Treatment with a rhythm control drug is appropriate when AF recurs within a few months of cardioversion The most realistic goal of antiarrythmic drug therapy in patient with persistent AF is to delay the onset of next episode by at least for several months, not for several years.

21. PHARMACOLOGICAL MANAGEMENT OF PATIENTS WITH NEWLY DISCOVERED Af

22. PHARMACOLOGICAL MANAGEMENT OF PATIENTS WITH RECURRENT PAROXYSMAL af

23. PHARMACOLOGICAL MANAGEMENT OF PATIENTS WITH RECURRENT PERSISTENT OR PERMANENT Af

24. If the patient is hemodynamically unstable then early transthoracic DC cardioversion is needed because a delay in cardioversion is never appropriate in setting of severe cardiovascular decompensation . If the patient is hemodynamically stable who present with AF that does not appear to be self limiting following management decisions to be made: Early Cardioversion : - Performed if AF duration is <48 hours - rapid relief of symptoms - Avoidance of need of thansoesophageal echocardiography - Avoidance of therapeutic anticoagulation for 3-4 weeks - Lower risk of early AF recurrence because of less atrial remodeling Delayed Caedioversion : - Duration of AF is >48 hours - Duration is unclear in non anticoagulated patient - Transoesophageal echocardiography not available - Left Atrial thrombus by TEE - Correctable causes of AF ( hyperthyroidism, achoholism )

25. In case if immediate cardioversion is needed then shock is to be given after loading dose of unfractionated heparin followed by continuous maintenance infusion as early as possible. But if delayed cardioversion is to be done then protocol to be used is 3 weeks anticoagulation cardioversion 4 weeks anticoagulation Post cardioversion anticoagulation is needed to prevent thromboembolism related to atrial stunning as atria take some time to gain its normal functioning. For DC cardioversion an appropriate first shock strength using a biphasic waveform is 150 - 200 J followed by higher output shocks if needed. But if a 360-J biphasic shock is unsuccessful then ibutilide is to be given before another shock to lower the defibrillation energy required and improve the success rate. Properly timed DC current with pads on anterior and posterior chest depolarized the heart, disrupting reenterant circuits and allowing sinus node to regain control of atria.It is important to “synchronize” the shock with ventriculaer depolarization ( R wave on ECG )

26. There are two types of failure : Complete failure Here sinus rhythm has not been restored so increasing the shock strength or ibutilide enhancement may turn it to be successful 1) Incomplete failure Here sinus rhythm is attained after shock with immediate recurrence of AF within a few seconds. In this case increasing the shock strength is useless, ibutilide infusion may help out

27. PHARMACOLOGICAL CARDIOVERSION Early pharmacological cardioversion can be tried in hemodynamically stable patients as it has advantage of not requiring anesthesia or deep sedation as well as lower probability of immediate recurrence of AF. “ pill-in-the-pocket ” i.e. episodic drug therapy was developed for patients with relatively infrequent episodes of AF by using flecainide (100-200mg) or propafenone (300-600 mg) including a short acting beta blocker or CCB for rate control.

28. Doses and safety consideration of drugs used for pharmacological cardioversion Drugs Doses Exclude / use with caution Vaughan Williams Class IA : Disopyramide Immediate release: 100- 200 mg once every 6 hr Extended release: 200 – 400 mg once every 12 hr HF, Prolonged QT interval, Glaucoma, Quinidine 324 – 648 mg every 8 hr Prolonged QT interval, Diarrhoea Procainamide 0.5 – 1 gm oral or IM F/B 0.25-0.5 gm every 2 hr or 500mg IV loading F/B 2mg/kg/hr. Maintenance dose 0.5gm every 4-6 hr Prolonged QT interval, SLE

29. Vaughan Williams Class IC Flecainide 50-200 mg once every 12 hr Sinus or V node dysfunction, HF, CAD, Atrial Flutter,Liver desease Propafenone Immediate release 150-300 mg once every 8hr. Extended release 225-425mg once every 12hr Sinus or V node dysfunction, HF, CAD, Atrial Flutter,Liver desease Vaughan Williams Class III Amiodarone Oral: 400-600 mg daily in divided doses for 2-4 wk; maintenance typically 100-200 mg QD, IV: 150 mg over 10 min then 1 mg/min for 6 hours then 0.5 mg /min for 18 hours or change to oral dosing, after 24 hours consider decreasing dose to 0.25mg/min Sinus/AV node dysfunction, infranodal conduction disease, lung disease, prolonged QT interval Dofetilide 125-500 mcg once every 12 hours Prolonged QT interval, Renal disease, Hypokalemia , Avoid other QT interval prolonging drugs

30. Dronedarone 400 mg once every 12 hours Bradycardia , HF, Long standing AF/ flutter, Liver disease, Prolonged QT interval Sotalol 40-160 mg every 12 hours Prolonged Qt interval, Renal Disease, Hypokalemia , HF, Asthma, Sinus / AV nodal dysfunction

31. Vernakalant It is an atrial selective antiarrythmic drug specially designed to block potassium channels at the atrial level without any proarrythmic effects at the ventricular level and is recommended for i.v . use. Its use has been advocated by European Society of Cardiology for rapid conversion of AF. But ACT-5 trial was suspended regarding the adverse effects of vernakalant which were hypotension, complete AV block and cardiogenic shock. Since then a lot of controversies are prevailing regarding its use and is still in PHASE- III trial. Dronaderone It has been associated with increased mortality in patients even with minimal heart failure which was well documented by ANDROMEDA trial . It is used only in europe now where also ESC does not considers it in heart failure. Pifenidone This is an antifibrotic drug which also potentiates L-type calcium channels has been recently found to be effective and is under study

32. ROLE OF STATINS, ACE INHIBITORS AND ARBs, omega-3 fatty acids, and Ranolazine Statins prevent AF because of their anti-inflammatory effects. But meta-analysis of randomized trials have concluded that statins do not prevent AF, except after open heart surgery ACE inhibitors and ARBs have favourable effects on electrical and structural remodeling and so prevent AF which is only limited to patients with left ventricular systolic dysfunction or hypertrophy Ranolazine blocks atrial selective late sodium channels and also inhibits L – type calcium channels as well as RyR2 receptor

33. MANAGEMENT STRATEGIES FOR MAINTAINING SINUS RHYTHM

34. NON PHARMACOLOGICAL METHODS Catheter ablation AV node ablation Implanted defibrillator Role of atrial pacing

35. CATHETER ABLATION It is difficult as AF arrhythmia substrate is usually widespread. But success rate is more than 95% if arrhythmia substrate is well defined, localized and temporally stable Ideal candidate is one with lone AF or only minimal structural heart disease and the person has symptomatic AF that is affecting quality of life and that has not adequately responded to drug therapy. Less successful if left atrium is markedly dilated or in case of persistent AF of more than 4 yrs duration Most commonly used technique is radiofrequency ablation using a 3.5 mm irrigated tip or an 8 mm tip catheter which includes electrical isolation of pulmonary veins which is accomplished by either ostial ablation or wide area ablation 1 to 2 cm away from the ostia , in the antral region of pulmonary veins Risk: Cardiac tamponade , Pulmonary vain stenosis , cerebral thromboembolism , atrioesophageal fistula

36. Different ablation strategies are : Linear ablation across the left atrial roof, mitral isthmus or cavotricuspid isthmus Ablation of CFAEs in left atrium, coronary sinus,or right atrium Combination of linear ablation and CFAEs ablation Ablation of ganglionated plexi Newer ablation tools have been discovered to cut short the lengthy procedure of point by point ablation required at large number of sites. These are : Cryobaloon catheter Laser balloon catheter High-density focused ultrasound balloon catheter High density mesh ablator Out of this cryoballoon catheter is most commonly used.

37. AV Node ablation AV node ablation result in complete AV nodal block and substitute a regular, paced rhythm for an irregular and rapid rhythm. Advantage with this is its usefulness in tachycardia induced cardiomyopathy by improving left ventricular ejection fraction, and disadvantage lies in lifelong need for ventricular pacing and no restoration of AV synchrony. Implanted defibrillator Most appropriate candidates for an implanted atrial defibrillator are patients with relatively infrequent episodes of poorly tolerated AF who do not respond well to pharmacological therapy, who are not good candidates for catheter ablation, and who qualify for an ICD. Limitations of atrial defibrillation are painful shocks and the potential for immediate recurrences of AF after cardioversion .

38. Atrial pacing Dual right atrial pacing of the interatrial septum in the region of Bachmann bundle prevents AF Different algorithms of pacing are to : Overdrive sinus rhythm Burst pacing Suppression of post extrasystolic pauses Acceleration of atrial pacing rate when repetitive premature atrial complexes are sensed. Antitachycardia pacing(ATP) which consists of a burst of rapid atrial pacing at the onset of AF may be useful for terminaton of atrial flutter or an atrial tachycardia, but is rarely if ever effective for AF. So due to insufficient evidence atrial pacing is not indicated for prevention of AF in patients without bradycardia .

39. SURGICAL TECHNIQUES MAZE PROCEDURE It is the most effective used surgical technique for AF. It is a cut-and-sew procedure in which 12 atrial incisions are given to isolate pulmonary veins and to create lines of block in the left atrium and right atrium. This procedure requires cardiopulmonary bypass and is technically difficult to perform so is not widely used. So gradual modifications were adopted in this technique with use of different types of energy for surgical ablation such as radiofrequency energy, cryoenergy , microwave, and high intensity focussed ultrasound. THE CORRIDOR PROCEDURE In this procedure an isolated strip of muscle is created which links the SA node and AV node, thus driving ventricle rate via AV node – His bundle complex. MINIMALLY INVASIVE PROCEDURES Complete endoscopic ablation with microwave energy Thoracoscopic or robotic assisted off pump epicardial microwave ablation Bilateral minithoracoscopic video assisted pulmonary vein ablation usiing bipolar radiofrequency, and others

40. Prevention of thromboembolic complication Major goal of therapy in patients with AF is to prevent thromboembolic complications notably stroke. But for this proper risk stratification and condition is needed to be identified for an appropriate anticoagulant or any other therapy. METHODS Anticoagulation Non-pharmacological The strongest predictors of ischemic stroke and systemic thromboembolism are history of stroke or TIA and mitral stenosis . For this a simple scheme form risk stratification was developed known as CHADS₂ score. But apart from this renal failure has also been considered as an independent risk factor.

41. In 2010 European guidelines proposed another way of risk stratification by recommending 3 additional risk factors as mentioned in CHADS₂ and was considered as CHA₂DS₂- VASc . Additional risk factors considered were presence of vascular disease, age 65-74 yrs and female gender with one score for each. Here total score was 9 and if score was ≥ 2 then oral anticoagulation was needed and if score was 1 then oral anticoagulation or aspirin should be used after risk benefit analysis.

42. CHA2DS2-VASc Score Congestive HF 1 Hypertension 1 Age > 75 years 2 Diabetes Mellitus 1 Stroke/TIA/TE 2 Vascular disease (prior MI, PAD, or aortic 1 plaque) Age 65–74 y 1 Sex category (i.e., female sex) 1 Maximum Score 9

43. ANTITHROMBOTIC THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION

44. RISK ASSESSMENT FOR BLEEDING Estimation of bleeding risk is a crucial step in the management of patients with atrial fibrillation (AF). Three bleeding risk–prediction schemes have been derived and validated exclusively in AF populations: HEMORR 2 HAGES HAS-BLED, and ATRIA Out of these most commonly used is the HAS-BLED score which has been discussed here

45. BLEEDING RISK SCORES VALIDATED IN AF PATIENTS

46. Drugs for prevention of thromboembolic complications Warfarin : It acts by interfering with synthesis of Vit -K dependent clotting factors in liver.It reduced risk of stroke by 61%. Target International normalized ratio 2-3. even relatively small decrease in INR level from 2 to 1.7 more than doubles the risk of stroke. Low- molecular weight heparin: Heparin, especially low-molecular weight heparin is typically used as a temporary bridge therapy to therapeutic anticoagulation when therapy with warfarin is initiated or in high-risk patients for a few days before and after a medical or dental procedurewhen anticoagulation with warfarin has been suspended No advantage on combination of warfarin and unfractionated heparin was noted . Direct thrombin inhibiters: Dabigatran - an oral direct thrombin inhibitor at a dose of 110mg twice daily was recently shown to have similar efficacy to warfarin (RELY trial) but lower rate of major hemorrage , also with an advantage of a fixed dosing and lesser effects from dietary factors

47. Factor Xa inhibitors: Rivaroxaban - an oral factor Xa inhibitor was approved by FDA in 2011 for stroke prevention in atrial fibrillation based on the conclusions of ROCKET-AF trial in which it was non inferior to warfarin in stroke prevention and had substantially less intracranial hemorrhage. It is dosed at 20 mg once a day with dose reduction to 15 mg in patients with creatinine clearance < 50 ml/min Apixaban - another oral factor Xa inhibitor is yet to be approved for atrial fibrillation. In ARISTOTLE trial I has shown a lower risk of major bleeding. According to AVERROES trial in patients not suitable for warfarin , apixaban was shown to be well tolerated and superior to aspirin. It is dosed at 5 mg twice daily with dose reductions in high risk category. ACTIVE-A trial advocated for combination of aspirin and clopidogrel for patients unable to take warfarin but it was associated with slightly increased risk of bleeding.

48. Dose selection of oral anticoagulants in patients with Chronic kidney disease Renal Function Warfarin Dabigatran Rivaroxaban Apixaban Normal/ mild impairment Dose adjusted for INR 2-3 150 mg BID CrCl >30ml/min 20 mg HS( CrCL >50ml/min) 5 or 2.5 mg BID Mod impairment Dose adjusted for INR 2-3 150 mg BID or 75 mg BID ( CrCl > 30ml/min 15 mg HS ( CrCL 30-50ml/min) 5 or 2.5 mg BID Sever impairment Dose adjusted for INR 2-3 75 mg BID ( CrCl 15-30 ml/min) 15 mg HS ( CrCl 15-30 ml/min) NR ES RD not on Dialysis Dose adjusted for INR 2-3 NR ( CrCl <15 ml/min) NR ( CrCl <15 ml/min) NR ESRD on Dialysis Dose adjusted for INR 2-3 NR ( CrCl <15 ml/min) NR ( CrCl <15 ml/min) NR

49. NON-PHARMACOLOGICAL METHODS EXCISION OF LEFT ATRIAL APPENDAGE CLOSURE OF LEFT ATRIAL APPENDAGE Approximately 90% of left atrial thrombi form in the left atrial appendage, so its better to remove the source. Both of these two techniques were compared and final conclusion was in favour of excision of the appendage as compared to percutaneous closure. In PROTECT AF trial they considered percutaneous closure of left atrial appendage with a filter device (watchman) which was found to be noninferior to warfarin for stroke prevention

50. ACC/ AHa new management guidline

51. Recommendations for Prevention of Thromboembolism in Patients With AF

52. Recommendations for rate control

53. Recommendation for rhythm control

54. Recommendation for antiarrhythmic drugs to maintain sinus rhythm

55. Class I 1 . Before initiating antiarrhythmic drug therapy, treatment of precipitating or reversible causes of AF is recommended. (Level of Evidence: C) 2 . The following antiarrhythmic drugs are recommended in patients with AF to maintain sinus rhythm , depending on underlying heart disease and comorbidities (Level of Evidence: A): a . Amiodarone b . Dofetilide c . Dronedarone d . Flecainide e . Propafenone f . Sotalol 3 . The risks of the antiarrhythmic drug, including proarrhythmia , should be considered before initiating therapy with each drug. (Level of Evidence: C) 4 . Owing to its potential toxicities, amiodarone should only be used after consideration of risks and when other agents have failed or are contraindicated. (Level of Evidence: C )

56. Class IIa 1 . A rhythm-control strategy with pharmacological therapy can be useful in patients with AF for the treatment of tachycardia-induced cardiomyopathy . (Level of Evidence: C) Class IIb 1 . It may be reasonable to continue current antiarrhythmic drug therapy in the setting of infrequent , well-tolerated recurrences of AF, when the drug has reduced the frequency or symptoms of AF. (Level of Evidence: C) Class III: Harm 1 . Antiarrhythmic drugs for rhythm control should not be continued when AF becomes permanent (Level of Evidence: C) including dronedarone (Level of Evidence: B) 2 . Dronedarone should not be used for treatment of AF in patients with New York Heart Association (NYHA ) class III and IV HF or patients who have had an episode of decompensated HF in the past 4 weeks . (Level of Evidence: B)

57. Management of AF in special group of patients

58. Thank you.