Classification :
• Paroxysmal (usually = 48h) → Recurrent
• Persistent (> 7d) → Recurrent
• Long-standing persistent (> 1y) → Permanent (accepted AF)
• Recurrent episodes of paroxismal AF cause atrial remodelling and the result will be persistent AF.

Atrial Remodelling :
• Cardiovascular disease → Structural changes: fibrosis, dilatation, reducing contractility → ACEI will slow this process
• Rapid atrial rate → Electrophysiological changes: reducing atrial APD, reducing atrial ERP ,Ion channel alterations → Antiarrythmic drugs
• The most important ionic current which play a role are Ca²+ , others K & rapid sodium current.

Reasons for Rhythm Control :
Intolerable Symptoms, AF duration < 1y., Young physically active, Paroxysmal AF, Good response to therapy, LA< 50mm, Contraindication to anticoagulation

Rhythm control & Cardioversion (ESC AF Guidelines 2016)

Anticoagulation in patients undergoing cardioversion
Cardioversion carries an inherent risk of stroke in nonanticoagulated patients, which is reduced substantially by the administration of anticoagulation. Immediate initiation of anticoagulation is important in all patients scheduled for cardioversion. Patients who have been in AF for longer than 48 h should start OAC at least 3 weeks before cardioversion and continue it for 4 weeks afterwards. OAC should be continued indefinitely in patients at risk of stroke. When early cardioversion is desired, TOE can exclude the majority of left atrial thrombi, allowing immediate cardioversion. Ongoing studies will inform about the safety and efficacy of newly initiated anticoagulation using NOACs in patients scheduled for cardioversion.

Electrical cardioversion
Synchronized direct current electrical cardioversion quickly and effectively converts AF to sinus rhythm, and is the method of choice in severely haemodynamically compromised patients with new-onset AF. Electrical cardioversion can be performed safely in sedated patients treated with intravenous midazolam and/or propofol. Continuous monitoring of blood pressure and oximetry during the procedure is important. Intravenous atropine or isoproterenol, or temporary transcutaneous pacing, should be available to mitigate post-cardioversion bradycardia. Anterior–posterior electrode positions generate a stronger shock field in the left atrium than anterolaterally positioned electrodes. Pre-treatment with amiodarone, sotalol, ibutilide, or vernakalant can improve the efficacy of electrical cardioversion, and similar effects are likely for flecainide and propafenone. Beta-blockers, verapamil, diltiazem, and digoxin do not reliably terminate AF or facilitate electrical cardioversion. When antiarrhythmic drug therapy is planned to maintain sinus rhythm after cardioversion, it seems prudent to start therapy 1–3 days before cardioversion to promote pharmacological conversion.

Stroke prevention therapy (ESC AF Guidelines 2016)

• OAC should be considered for men with a CHA2DS2-VASc score of 1 and women with a score of 2, balancing the expected stroke reduction, bleeding risk, and patient preference. Importantly, age (65 years and older) conveys a relatively high and continuously increasing stroke risk that also potentiates other risk factors (such as heart failure and sex).


Antiarrhythmic drug therapy for prevention of AF

To Make The Right Choice For Prevention of AF :
Lone AF → Flecainide
LVH → Dronedarone
CAD → Sotalol
HF → Amiodarone
Vagally mediated AF / HCM → Disopyramide
Cardiovascular disease → ACEIs, Statin

• Dronedarone 33-39%, Flecainide 34-42%, Propafenone 35-40%, Sotalol 37-50%, Disopyramide 44-54%, Amiodarone 50-78%, Dofetilide 66-71% (Review article, John Camm, International Journal of Cardiology 155, 2012)
• The rates of maintaining sinus rhythm at 1 year for sotalol are 30% to 50%. (Lafuente-Lafuente C...et al. 2007)
• Sotalol prevents recurrent AF as effectively as the fixed dose quinidine – verapamil combination, but less effectively than amiodarone. (European Heart Journal 2010)

ESC guideline algorithm for long-term therapy
Selection of antiarrhythmic drugs for long-term therapy: safety first!

Prevent recurrent AF in patients with HCM
• Class IIa recommendation; Amiodarone or disopyramide combined with a beta blocker or nondihydropyridine calcium channel antagonists are reasonable for therapy. Class IIb recommendation; Sotalol, dofetilide, and dronedarone may be considered for a rhythm-control strategy in patients with HCM. (AHA/ACC/HRS Guideline 2014)
• Beta-blockers and diltiazem or verapamil seem reasonable treatment options for rate control in these patients. In the absence of significant LV outflow tract obstruction, digoxin can be used alone or in combination with beta-blockers. Amiodarone seems a safe antiarrhythmic drug in AF patients with hypertrophic cardiomyopathy, and expert opinion suggests that disopyramide may be beneficial in those with outflow tract obstruction. AF ablation is effective to suppress symptomatic AF recurrences. (ESC AF Guidelines 2016)

AF attack in WPW
• Intravenous procainamide, propafenone, or ajmaline can be used to acutely slow ventricular rate, whereas digoxin, verapamil, and diltiazem are contraindicated. Intravenous amiodarone should be used with caution, as there are case reports of accelerated ventricular rhythms and ventricular fibrillation in patients with preexcited AF receiving intravenous amiodarone infusion. (ESC AF Guidelines 2016)
• Unlike many other AADs Flecainide is safe & effective for termination of AF in patient with WPW syndrome. (AF –the Role of Flecainide, Fifth edition, edited by MJ Pekka Raatikainen, MD)
• In patients with pre-excitation and AF, digoxin, nondihydropyridine calcium channel antagonists, or intravenous amiodarone should not be administered as they may increase the ventricular response and may result in ventricular fibrillation. (AHA/ACC/HRS Guideline 2014)

ESC recommendations for inherited cardiomyopathies

Atrial fibrillation & Heart failure (ESC AF Guidelines 2016)

With reduced ejection fraction (HFrEF)
• For rate control only beta-blockers and digoxin are suitable in HFrEF because of the negative inotropic potential of verapamil and diltiazem. Beta-blockers are usually the first-line option in patients with clinically stable HFrEF.
• The diagnosis of tachycardiomyopathy can be challenging, and at times requires the restoration of sinus rhythm. Catheter ablation may be a useful method to restore LV function and quality of life in AF patients with HFrEF.

With preserved ejection fraction (HFpEF)
• The diagnosis of HFpEF in patients with AF is problematic because of the difficulty in separating symptoms that are due to HF from those due to AF. Echocardiography can support the detection of HFpEF in patients with symptomatic AF by providing evidence of relevant structural heart disease [e.g. LVH] and/or measurement of diastolic dysfunction.
• The management of patients with AF and concomitant HFpEF should focus on the control of fluid balance and concomitant conditions such as hypertension and myocardial ischaemia.

Ablation of AF in HF patients
• Catheter ablation, compared with amiodarone therapy, significantly reduces recurrent AF in AF patients with HFrEF. Selected patients with HFrEF and AF can achieve recovery of LV systolic function after catheter ablation (probably reflecting tachycardiomyopathy)(Especially in patients without a previous myocardial infarction).

Valvular heart disease & Echocardiography

From ESC AF guidelines 2016;

Approximately 30% of patients with AF have some form of valvular heart disease, often detected only by echocardiogram. Valvular heart disease can be associated with an increased thrombo-embolic risk, which probably also adds to the stroke risk in AF patients.

Similar to heart failure, valvular disease and AF interact with and sustain each other through volume and pressure overload, tachycardiomyopathy, and neurohumoral factors.

Valvular AF mainly refers to AF patients that have either rheumatic valvular disease (predominantly mitral stenosis) or mechanical heart valves. In fact, while AF implies an incremental risk for thrombo-embolism in patients with mitral valve stenosis, there is no clear evidence that other valvular diseases, including mitral regurgitation or aortic valve disease, need to be considered when choosing an anticoagulant or indeed to estimate stroke risk in AF.

When valve dysfunction is severe, AF can be regarded as a marker for progressive disease, thus favouring valve repair or replacement.

The role of echocardiographic imaging among patients with AF
• Nearly all patients presenting with their first episode of AF will benefit from TTE evaluation of left atrial size, left ventricular systolic function, and mitral valve morphology and function. Especially it is indicated if there is any sign of structural disease, heart failure or heart murmur. Also it is indicated prior to starting an antiarrhythmic drug for prevention AF.
• A more selected subgroup may benefit from the additional information obtained from TEE evaluation for left atrial thrombi to allow for early cardioversion if no thrombi are identified. For example when there are significant heart failure findings because of AF, early cardioversion maybe is indicated.
• Studies from the Stroke Prevention in Atrial Fibrillation (SPAF) investigators confirmed the usefulness of TEE for predicting thromboembolism. The rate of stroke was increased over threefold when TEE evidence of dense spontaneous echocontrast was present, increased by threefold for reduced left atrial appendage peak ejection flow velocity and for left atrial appendage thrombus, and increased by fourfold by complex aortic plaque.

Combination therapy with oral anticoagulants and antiplatelets

A recent meta-analysis involving 30 866 patients with a recent ACS evaluated the effects of adding NOAC therapy to single (4135 patients) or dual (26 731 patients) antiplatelet therapy. The addition of a NOAC increased the bleeding risk by 79–134%, while reducing recurrent ischaemic events only marginally in patients without AF. OAC monotherapy, and not combination therapy with antiplatelets, is recommended in AF patients with stable CAD but without an ACS and/or coronary intervention in the previous 12 months.

The optimal combination antithrombotic therapy or duration of combination therapy for AF patients undergoing percutaneous coronary intervention is not known, but the continued bleeding risk suggests a short duration. Expert consensus, reviewed and reconsidered by this Task Force, suggests the following principles:

In general, a short period of triple therapy (OAC, aspirin, clopidogrel) is recommended, followed by a period of dual therapy (OAC plus a single antiplatelet). When a NOAC is used, the consensus recommendation is that the lowest dose effective for stroke prevention in AF should be considered. The use of prasugrel or ticagrelor as part of triple therapy should be avoided unless there is a clear need for these agents (e.g. stent thrombosis on aspirin plus clopidogrel), given the lack of evidence and the greater risk of major bleeding compared with clopidogrel.

The omission of aspirin while maintaining clopidogrel and OAC has been evaluated in the WOEST trial, in which 573 anticoagulated patients undergoing percutaneous coronary intervention (70% with AF) were randomized to either dual therapy with OAC and clopidogrel (75 mg once daily) or to triple therapy with OAC, clopidogrel, and aspirin. Bleeding was lower in the dual vs. triple therapy arm, driven by fewer minor bleeding events. The rates of myocardial infarction, stroke, target vessel revascularization, and stent thrombosis did not differ (albeit with low event numbers), but all-cause mortality was lower in the dual therapy group at 1 year (2.5% vs. triple therapy 6.4%). Although the trial was too small to assess ischaemic outcomes, dual therapy with OAC and clopidogrel may emerge in the future as an alternative to triple therapy in patients with AF and ACS and/or coronary intervention.

Pregnancy (ESC AF Guidelines 2016)

Rate control
Owing to a lack of specific data, beta-blockers, verapamil, diltiazem, and digoxin all carry a US Food and Drug Administration pregnancy safety category of C (benefits may outweigh risk), except for atenolol (categoryD: positive evidence of risk). Their use should be at the lowest dose and for the shortest time required. None of the agents are teratogenic, but they readily cross the placenta. Beta-blockers are commonly used in pregnant women with cardiovascular conditions (e.g. for management of gestational hypertension and pre-eclampsia), but may be associated with intrauterine growth retardation, and hence growth scans after 20 weeks' gestation are recommended. Digoxin is considered safe for maternal and foetal arrhythmias. There are insufficient data to comment on verapamil or diltiazem, hence rate control using beta-blockers and/or digoxin is recommended. With regards to breastfeeding, all rate control agents are present in breast milk, although levels of beta-blockers, digoxin, and verapamil are too low to be considered harmful. Diltiazem will be present at high levels and should be considered second-line treatment.

Rhythm control
Amiodarone is associated with severe adverse foetal side-effects and should only be considered for emergency situations. Flecainide and sotalol can both be used for conversion of foetal arrhythmias without major adverse effects, and thus are likely to be safe to treat maternal symptomatic AF. Electrical cardioversion can be effective for restoration of sinus rhythm when tachyarrhythmia is causing haemodynamic instability, with low rates of adverse outcomes for both mother and foetus. However, in view of the risk of foetal distress, electrical cardioversion should only be carried out where facilities are available for foetal monitoring and emergency caesarean section. As with other emergencies during pregnancy, patients should receive 100% oxygen, intravenous access should be established early, and the mother should be positioned in the left lateral position to improve venous return.

VKAs should be avoided in the first trimester because of teratogenic effects, and in the 2–4 weeks preceding delivery to avoid foetal bleeding. Low-molecular-weight heparins are a safe substitute, as they do not cross the placenta. Pregnant patients with AF and mechanical prosthetic valves who elect to stop VKA treatment in consultation with their specialist team between 6–12 weeks of gestation, should receive continuous, dose-adjusted unfractionated heparin or dose-adjusted subcutaneous low-molecular-weight heparin.

AF in pregnant women is rare and is usually associated with preexisting heart disease. AF is associated with increased complications for the mother and foetus. Pregnant women with AF should be managed as high-risk pregnancies.

Other points of ESC guidelines 2016

Pill in the pocket' cardioversion performed by patients
In selected patients with infrequent symptomatic episodes of paroxysmal AF, a single bolus of oral flecainide (200–300 mg) or propafenone (450–600 mg) can be self-administered by the patient at home ('pill in the pocket' therapy) to restore sinus rhythm, after safety has been established in the hospital setting.

Bridging periods off oral anticoagulation
Most cardiovascular interventions (e.g. percutaneous coronary intervention or pacemaker implantation) can be performed safely on continued OAC. When interruption of OAC is required, bridging does not seem to be beneficial, except in patients with mechanical heart valves.

Do not!
Do not use antiplatelet therapy for stroke prevention in AF.
Do not permanently discontinue oral anticoagulation in AF patients at increased risk of stroke unless such a decision is taken by a multidisciplinary team.
Do not use rhythm control therapy in asymptomatic AF patients, nor in patients with permanent AF.
Do not perform cardioversion or catheter ablation without anticoagulation, unless an atrial thrombus has been ruled out transoesophageal echocardiogram.

LAA occlusion After stroke


Recommendations for preventing postoperative atrial fibrillation
Amiodarone or vernakalant have been efficient in converting post-operative AF to sinus rhythm.
In asymptomatic patients and in those with acceptable symptoms, rate control or deferred cardioversion preceded by anticoagulation is a reasonable approach.



Compilation by Dr. Samad Ali Moradi, According to Guidelines & author work experience.