AF –pathophysiology and medical management Dipin.S Junior resident medicine

Supraventricular tachy arrythmia charecterised by uncoordinated atrial activation and consequent deterioration of atrial mechanical function.

ECG -rapid fibrillatory waves with changing morphology and rate and a ventricular rhythm that is irregularly irregular Usually originates near the pulmonary veins

Classification of AF Diagnosis of AF New Onset AF Paroxysmal Up to 7 d Persistent > 7 days Permanent CV failed

Types of Atrial Fibrillation Paroxysmal AF: if it terminates spontaneously in fewer than 7 days (often in <24 h). Persistent AF: when it terminates either spontaneously after 7 days or following cardio version. Permanent AF: cardio version has failed or not attempted Recurrent : after 2 or more episodes

developed world- the most common causes are hypertension and coronary artery disease developing countries -hypertension, rheumatic valvular heart disease, and congenital heart disease are the most causes Presence of CHF markedly increases risk of AF

factors Factors that trigger Factors that perpetuate Triggering foci of rapidly firing cells within the sleeve of atrial myocytes extending into the pulmonary veins - shown to be the underlying mechanism of most paroxysmal AF

The pulmonary veins of patients with paroxysmal AF demonstrate abnormal properties of conduction Markedly reduced effective refractory period within the pulmonary veins Progressive conduction delay within the pulmonary vein in response to rapid pacing or programmed stimulation Conduction block between the pulmonary vein and the LA Heterogeneity of conduction promotes reentry within PV

Other foci- the superior vena cava, the ligament of Marshall, the musculature of the coronary sinus, left atrial wall, crista terminalis of right atria Prior to initiation-Primary increase in adrenergic tone followed by a marked vagal predominance (paroxysmal AF) Vagal stimulation shortens the refractory period of atrial myocardium with a nonuniform distribution .

perpetuation The multiple wavelet hypothesis(More and colleagues) Fractionation of wavefronts traversing the atria into daughter wavelets. The number of wavelets at any moment depends on the refractory period, conduction velocity, and anatomic obstacles in different portions of the atria.

Interstitial fibrosis predisposes to intraatrial reentry and AF(Li and colleagues) Delayed interatrial conduction and inhomogeneous dispersion of atrial refractory periods Long-standing AF -loss of myofibrils, accumulation of glycogen granules, disruption in cell-to-cell coupling at gap junctions,and organelle aggregates

AF itself produces alterations of atrial architecture that further contribute to atrial remodeling, mechanical dysfunction, and perpetuation of fibrillation.

Myocardial stretch is an important mechanism of AF in the elderly. Altered stretch on atrial myocytes results in opening of stretch-activated channels.(L type Ca) AF produces electrical remodeling that promotes further AF.

haemodynamics Loss of atrial contraction A rapid ventricular rate An irregular ventricular rhythm Loss of mechanical AV synchrony affects ventricular filling esp. when left ventricle has reduced compliance.

The loss of AV synchrony results in a decrease in LVEDP (as the loading effect of atrial contraction is lost) Stroke volume and LV contractility are reduced (Frank starlings principle) Although there is a reduction in the LVEDP, there is an increase in the left atrial mean diastolic pressure

Patients with restrictive physiology- pulmonary edema and hypotension may occur with AF In dilated cardiomyopathy – min. hemodynamic compromise if LV compliance is not affected . Patients with heart failure do worse when in AF 1st clinical manifestation of AF may be CHF related to a tachycardia-induced cardiomyopathy.

thromboembolism Thrombi mostly arise within the left atrial appendage Flow velocity in left atrial appendage is reduced during AF Nitric oxide (NO) production in the left atrial endocardium is reduced Increase in levels of the prothrombotic protein plasminogen activator inhibitor 1

Objectives of Treatment Relief of Symptoms & Prevent recurrence-correction of rhythm disturbance Prevention of Systemic Thromboembolism Tachycardia induced Myocardial Remodeling-rate control

CHADS2 Scoring One Point Cardiac Failure Hypertension Age more than 75 Diabetes Two Points Stroke or TIA, STE

CHADS2 based Stroke Incidence CHADS2 Score (points) Adjusted Stroke Incidence % per year 1.9 1 2.8 2 4.0 3 5.9 4 8.5 5 12.5 6 18.2 Non valvular Atrial Fibrillation Rx with anticoagulation

Risk Stratification Risk Factor Stratification Risk Factors to be Ascertained High Risk Factors Prior Stroke/TIA or STE Event Mitral stenosis , prosthetic valve Moderate Risk Factors Age >75, HF, HT, EF <35%, DM Weaker Risk Factors Female, CAD,  Thyroid, 65- 74 yrs

Antithrombotic Therapy for Patients With Atrial Fibrillation

68% risk reduction with warfarin compared to placebo Target INR 2.5(2-3) Not only reduces frequency but severity and risk of death also. Relative risk reduction of 22% with aspirin compared to placebo No difference in the indications for antithrombotic therapy between paroxysmal, persistent or permanent AF.

Cardioversion antiarrhythmic drugs or the direct-current approach AF of <48 hours can be cardioverted without prior anticoagulation anticoagulation therapy is recommended for AF of uncertain duration.

2 strategies Oral warfarin with a therapeutic INR (2–3) for 3 to 4 weeks before cardioversion followed by continued warfarin thereafter Transesophageal echocardiography (TEE) and heparin immediately before cardioversion followed by oral warfarin thereafter. Left atria – stunning effect. So anticoagulation is to be continued for 4 wks

Direct current cardioversion Anteriorly and posteriorly placed electrodes Synchronized to QRS complex Initial shock energy of 200J preferred ( higher energy less chance of VF) In AF> 3 mnths antiarrythmic drug started before cardioversion to prevent immediate or early reccurance

AF lasting <1 wk – cardioversion -using oral flecainide, propafenone, dofetilide, and intravenous ibutilide. For longer duration- iv dofetilide( also amiodarone and ibutilide may be useful) Single oral dose of propafenone or flecainide – in recent onset AF (pill in the pocket)

Rate control vs rhythm control The choice of strategy is determined by : paroxysmal or persistent AF severity and type of symptoms associated cardiac and other medical diseases age of patient short- and long-term treatment goals choice of pharmacologic or nonpharmacologic therapy Try and maintain sinus rhythm in younger patients with AF In the elderly, if symptoms can be controlled with a rate strategy, it is preferred. Anticoagulation is needed in patients at high risk for stroke regardless of whether a rate or rhythm strategy is chosen.

Major Trials Comparing Rhythm Strategy and Rate Strategy Major trials include: AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management ) RACE (rate control versus electrical cardioversion) PIAF (pharmacological intervention in AF) AF-CHF Major overall findings: Rhythm-control strategy was not superior to rate-control strategy in terms of morbidity/mortality Appropriate choice of therapy should be based on each patient’s symptoms and disease rate control, prevention of thromboembolism, and correction of the rhythm disturbance - these strategies are not mutually exclusive Several studies have compared rate control and rhythm control in patients with AFib. Major trials include AFFIRM, RACE, PIAF, STAF, HOT CAFÉ, and AF-CHF.1-6 There were no differences in the primary end points in any of these studies. All the investigators concluded that rhythm control is not superior to rate control for the prevention of morbidity and mortality due to cardiovascular disease. However, it is important to keep in mind that appropriate therapy should be considered based on patient presentation, risk factors, and risk benefit ratio of the therapeutic option.1-6 The next 2 slides examine each of these trials in greater detail. The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833; Van Gelder IC, et al. N Engl J Med. 2002;347:1834-1840; 3. Hohnloser SH, et al. Lancet. 2000;356:1789-1794; 4. Carlsson J, et al. J Am Coll Cardiol. 2003;41:1690-1696; 5. Opolski G, et al. Chest. 2004;126:476-486; 6. Roy D, et al. N Engl J Med. 2008;358:2667-2677; 7. Fuster V, et al. Circulation. 2006;114:e257-e354. 1. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347:1825-1833. 2. Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834-1840. 3. Carlsson J, Miketic S, Windeler J, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003;41:1690-1696. 4. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation - Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 2000;356:1789-1794. 5. Opolski G, Torbicki A, Kosior DA, et al. Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest. 2004;126(2):476-486. 6. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358:2667-2677.

Control of ventricular rate In the acute phase, iv diltiazem, metoprolol, esmolol, or verapamil (slowing of AV nodal conduction within 5 minutes) Iv digoxin is less useful In chronic phase- digoxin gives good control of resting heart rate Beta blockers and CCBs during exercise. Chronically elevated vent. Rates despite drug therapy- AV nodal ablation

Maintenance of sinus rythm Avoidance of inciting factor Safety first principle in selecting antiarrythmics Class Ic drugs are to combined with AV nodal blockers Monitor QRS duration with class Ic(150% increase-reduce drug) Monitor QT interval with sotalol and amiodarone

Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation

Other drugs ACE inhibitors ARBs Reduce atrial fibrosis and promote favourable hemodynamics

Pharmacological management of patients with newly discovered atrial fibrillation AF

Pharmacological management of patients with recurrent paroxysmal atrial fibrillation (AF)

Pharmacological management of patients with recurrent persistent or permanent atrial fibrillation (AF)