AF –pathophysiology and medical management

Dipin.SJunior 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

Diagnosis of AF

New Onset AF

Paroxysmal Up to 7 d

Persistent > 7 days

Permanent CV failed

Classification of AF

• 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

Types of Atrial Fibrillation

• 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

Relief of Symptoms & Prevent recurrence-correction of rhythm disturbance

Prevention of Systemic Thromboembolism

Tachycardia induced Myocardial Remodeling-rate control

Objectives of Treatment

• Cardiac FailureOne Point

• HypertensionOne Point

• Age more than 75One Point

• DiabetesOne Point

• Stroke or TIA, STETwo Points

CHADS2 Scoring

CHADS2 Score (points)

Adjusted Stroke Incidence % per year

0 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

CHADS2 based Stroke Incidence

Risk Factor Stratification

Risk Factors to be Ascertained

High Risk FactorsPrior Stroke/TIA or STE EventMitral stenosis , prosthetic valve

Moderate Risk Factors Age >75, HF, HT, EF <35%, DM

Weaker Risk Factors Female, CAD, Thyroid, 65- 74 yrs

Risk Stratification

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

1. The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833; 2. 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.

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)