AF – pathophysiology and medical management

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

2. Supraventriculartachyarrythmiacharecterised by uncoordinated atrial activation and consequent deterioration of atrial mechanical function.

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

4. Classification of AF

5. 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

6. 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

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

8. 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

9. Other foci- the superior vena cava, the ligament of Marshall, the musculature of the coronary sinus, left atrial wall, cristaterminalis 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 .

10. 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.

11. Interstitial fibrosis predisposes to intraatrialreentry 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

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

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

14. 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.

15. 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

16. 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.

17. 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 atrialendocardium is reduced • Increase in levels of the prothrombotic protein plasminogen activator inhibitor 1

18. Objectives of Treatment

19. CHADS2 Scoring

20. CHADS2 based Stroke Incidence

21. Risk Stratification

22. Antithrombotic Therapy for Patients With Atrial Fibrillation

23. 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.

24. 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.

25. 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

26. 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 mnthsantiarrythmic drug started before cardioversion to prevent immediate or early reccurance

27. 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)

28. 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.

29. 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 • 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.

30. 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

31. 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

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

33. Other drugs • ACE inhibitors ARBs • Reduce atrial fibrosis and promote favourablehemodynamics

34. Pharmacological management of patients with newly discovered atrial fibrillation AF

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

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