Mechanisms & management of atrial fibrillation

Atrial fibrillation

1. Mechanisms & management of atrial fibrillation -ROHIT WALSE SENIOR RESIDENT DM CARDIOLOGY SCTIMST

2. SCOPE INTRODUCTION CLASSIFICATION MECHANISM- TRIGGERS SUBSTRATE MANAGEMENT RECOMMENDATIONS

3. INTRODUCTION Definition- Supraventricular tachyarrhythmia with uncoordinated atrial activation  ineffective atrial contraction ( ECG) characteristics- 1) Irregular R-R intervals 2) Absence of distinct repeating P waves and 3) Low amplitude baseline oscillations ( fibrillatory waves), f waves – 300-600 bpm

4. INTRODUCTION Ventricular rate during AF- 100-160 bpm WPW syndrome- ventricular rate > 250 bpm Patients with pacemaker and patients with 3 rd degree heart block with regular escape rhythm- ventricular rhythm may be regular

5. Sinus rhythm  Atrial fibrillation

6. Classification of AF

7. Coumel triangle summarizing the different contributors to AF

8. Electrophysiology of AF Trigger: Rapidly firing focus that can act as an initiator for the arrhythmia Substrate: Electrophysiological, mechanical and anatomical characteristics of the atria that sustain AF. Electrical remodeling – changes in properties of ion channels Structural remodeling – alteration in tissue architecture Macroscopic-Atrial dilatation Microscopic-Fibrosis

9. Basic atrial electrophysiology APD & RF are shorter in the atria (particularly in the left atrium) compared with the ventricular myocardium Regional heterogeneity within and between the atria Differences in Intra-atrial ion channel density

10. Triggers for AF Muscular sleeves : Extension of Left atrial myocardium over PVs Muscular sleeves within the pulmonary vein (PV) ostia are the source of the ectopic beats triggering AF in many patients with paroxysmal AF. Superior PVs have longer and better-developed myocardial sleeves than inferior PVs  most of the ectopic foci that initiate AF are from the superior PVs Regional Difference of ERPs Distal PVs have short ERPs compared to Proximal PVs (differences in ERP between proximal and distal PVs were decreased after isoproterenol infusion)

11. Ectopic focus Paroxysmal AF Superior PVs > Inferior PVs Distal PVs > Proximal PVs

12. Non-PV triggers Superior vena cava Coronary sinus Left atrial appendage Vein of marshall Crista terminalis Left atrial posterior free wall Myocardial sleeves Fibrosis P/catheter ablation procedure

13. Ganglionated plexi , which are conglomerations of autonomic ganglia on the epicardial surface of the heart, may play a role in the initiation and maintenance of AF Afterdepolarizations and extra-systolic activity DADs EADs

14. DADs Ionic Mechanisms. RyR2 channel abnormally remains open in diastole NCX activity enhanced

15. EADs Strong simultaneous discharge of vagal and sympathetic nerves ( vagosympathetic discharge) Vagal discharge   APD   (RP) Sympathetic stimulation   Ca2+ transients   cytoplasmic free Ca2+ during AP

16. Arrhythmic mechanisms that sustain AF

17. Arrhythmic mechanisms that sustain AF 1. Multiple wavelet hypothesis 2. Localized AF drivers Anatomical reentry Functional reentry Leading circle concept Spiral wave reentry / rotor concept

18. 1. Multiple wavelets Fibrillation is maintained by the irregular wandering of numerous wavelets generated by the fractionation of a wave front passing through tissue in a state of inhomogeneity with respect to excitability and conduction velocity

19. 2. Localized AF drivers

20. Dimension of circuit = wavelength (WL) = RP(Refractory period) × CV (conduction velocity) smallest circuit which can sustain functional reentry Leading Circle Model

21. S tability of AF according to the leading circle concept is determined by the number of simultaneous re-entry circuits that the atria can accommodate When the 1) WL is short (as a result of reduced RP or CV) or 2 ) when the atria are enlarged, more re‑entrant circuits can be accommodated and AF is more likely to maintain itself Why Atrial Enlargement Predisposes to AF?

22. Functional Reentry Due to Rotors/Spiral Waves Wavefront has a curved or spiral form , and the wavefront and wavetail meet at a focal point called a phase singularity (PS) Wavefront velocity in a rotor is not constant , depending instead on wavefront curvature due to current source–sink mismatch

23. Functional Reentry Due to Rotors/Spiral Waves Wavefront in close proximity to the PS is the region of highest curvature  area of slowest w avefront conduction velocity At the PS, the wavefront curvature is so high and conduction velocity is so slow, that the propagating wavefront is unable to invade a core of tissue in the centre of the rotor This tissue core  effectively unexcitable  forms an area of functional block similar to the centre of a leading circle reentrant circuit.

24. Reentry Circuit Rotor A reentrant circuit in the leading circle model must remain fixed in space because the centre of the circuit is completely unexcitable A rotor is able to move through space and, due to constant source–sink current mismatch at the PS and core, under certain circumstances the rotor can meander in various complex forms which in turn have important effects on rotor behavior and sustainability

25. SUBSTRATE Electrical Remodelling Structural Remodeling Autonomic or Neural remodeling

26. Electrical remodeling

27. Atrial Tachycardia Remodeling Decrease in atrial effective refractory period (ERP) and reduction in physiological ERP rate adaptation This ERP decrease reduces the wavelength, and thus atrial tachycardia remodeling produces a substrate favorable for AF Atrial tachycardia suppresses atrial myocyte contractility, by altering Ca2+ homeostasis and thereby causes “contractile remodeling ” that may contribute to atrial stasis and the associated thromboembolic predisposition, as well as to AF perpetuation

28. CHF and Atrial Structural Remodeling Atrial ERP is unchanged or increased by CHF, but local atrial conduction abnormalities occur in association with marked fibrosis between and within atrial muscle bundles A bnormalities in atrial structure and local conduction  stabilize atrial reentry  allow AF-sustaining reentry circuits that sometimes appear to have a stable macro-reentry pattern Ionic Mechanisms. NCX activity enhanced in CHF Delayed afterdepolarisation

29. F ibrosis A ction potential shortening occurs within about 10 days and coincides with the initial spontaneous maintenance of AF, but that atrial fibrosis then occurs over a period of up to a year, coinciding with long-standing persistence

30. Structural remodelling fatty infiltration inflammatory infiltration necrosis and amyloid deposition Adipose tissue has a paracrine effect through the release of adipokines with profibrotic properties . It also forms barriers to wavefront conduction and favour reentrant circuits

31. Autonomic and neural remodeling I ncrease in the density of sympathetic and parasympathetic innervation with AF After MI and cardiomyopathy Supported by the circadian variation of the paroxysmal AF episodes morning and a second rise in the evening fewer episodes on Saturdays more arrhythmias occurred during the last months of each year

32. RISK FACTORS FOR AF

33. Symptoms palpitations, fatigue, dizziness, light-headedness and dyspnoea Symptoms are absent in elderly Pulse Ecg Physical examination Exclude valvular heart disease Thyrotoxicosis HF alcohol consumption, obstructive sleep apnoea, obesity, hypertension, diabetes and pulmonary disease chest radiograph is recommend to exclude pulmonary disease and heart failure, thyroid-stimulating hormone to exclude thyrotoxicosis and a transthoracic echocardiogram should be performed to detect underlying structural heart disease, assess cardiac function and evaluate atrial size

34. WHOM TO SCREEN ? Opportunistic screening for AF by pulse taking or ECG rhythm strip is recommended in patients >_65 years of age. (Class I B)

35. Prevention Hypertension, diabetes and heart failure are three important conditions that predict future AF, so prevention or better treatment of these conditions might prevent the onset of new AF Rheumatic heart disease Obesity , high and low extremes of physical activity, excessive alcohol intake and obstructive sleep apnoea AF occurs in approximately one-quarter to one-third of patients who have had coronary bypass surgery. S tatins have shown some evidence for reducing incident AF in meta-analyses of population studies

36. ‘A’ Anticoagulation/Avoid stroke ‘B’ Better symptom control ‘C’ Cardiovascular risk factors and concomitant diseases: detection and management Management: the integrated ABC Pathway

37. ‘A’ Anticoagulation/Avoid stroke Stroke risk assessment Bleeding risk assessment Stroke prevention therapies Management of anticoagulation related bleeding risk

38. Stroke risk assessment Low risk: CHA2DS2-VASc score of 0 in men and 1 in women) who do not need any antithrombotic therapy High risk: CHA2DS2-VASc score of ≥1 in men and ≥2 in women)

39. ‘B’ Better symptom control Rate control Rhythm control Cardioversion AF ablation

40. Rate control TRIAL STRATEGY JOURNAL N; DURATION RESULTS AFFIRM TRIAL Rate control vs rhythm control NEJM, 2002 ( Multicentric ) 2027(Rate c) vs 2033(Rhythm c) 5yrs f/u -Mortality (p-0.08) -Continuous OAC (AF SR) RACE II TRIAL Rate control : Lenient (HR<110) vs Strict (<80@rest;<110 during moderate exrcise ) NEJM, 2010 311(Lenient) vs 303(Strict) 3 yr f/u -Similar MACCE (12.9%) -Lenient vs (14.9%) -S trict (p<0.001 for non inferiority)

41. Rhythm control In patients who present with an episode of AF, more than two-thirds have spontaneous conversion to sinus rhythm

42. Indications for rhythm control Based on the currently available evidence from RCTs, the primary indication for rhythm control is to reduce AF-related symptoms and improve QoL

43. CARDIOVERSION Acute rhythm control can be performed as an emergency cardioversion in a haemodynamically unstable AF patient . Synchronized direct current electrical cardioversion is the preferred choice in haemodynamically compromised AF patients as it is more effective than pharmacological cardioversion and results in immediate restoration of sinus rhythm. In stable patients , either pharmacological cardioversion or electrical cardioversion can be attempted; pharmacological cardioversion is less effective but does not require sedation.

44. Electrical cardioversion Electrical cardioversion can be performed safely in sedated patients treated with i.v. midazolam and/or propofol or etomidate. BP monitoring and oximetry during the procedure should be used routinely. Skin burns may occasionally be observed. Intravenous atropine or isoproterenol, or temporary transcutaneous pacing, should be available in case of post-cardioversion bradycardia. Biphasic defibrillators are standard because of their superior efficacy compared with monophasic defibrillators. Anterior posterior electrode positions restore sinus rhythm more effectively, while other reports suggest that specific electrical pad positioning is not critically important for successful cardioversion.

45. Pharmacological cardioversion Pharmacological cardioversion to sinus rhythm is an elective procedure indicated in haemodynamically stable patients. Its true efficacy is biased by the spontaneous restoration of sinus rhythm within 48 h of hospitalization in 76 - 83% of patients with recent onset AF (10 - 18% within first 3 h, 55 - 66% within 24 h, and 69% within 48 h). Therefore, a ‘wait-and-watch’ strategy (usually for <24 h) may be considered in patients with recent-onset AF as a non-inferior alternative to early cardioversion.

46. The choice of a specific drug is based on the type and severity of associated heart disease, and pharmacological cardioversion is more effective in recent onset AF. Flecainide (and other class Ic agents), indicated in patients without significant LV hypertrophy ( LVH ), LV systolic dysfunction, or ischaemic heart disease, results in prompt (3 - 5 h) and safe restoration of sinus rhythm in >50% of patients While i.v. amiodarone , mainly indicated in HF patients, has a limited and delayed effect but can slow heart rate within 12 h. Intravenous vernakalant is the most rapidly cardioverting drug, including patients with mild HF and ischaemic heart disease, and is more effective than amiodarone or flecainide

47. In selected outpatients with rare paroxysmal AF episodes, a self administered oral dose of flecainide or propafenone is slightly less effective than in-hospital pharmacological cardioversion but may be preferred (permitting an earlier conversion), provided that the drug safety and efficacy has previously been established in the hospital setting. An atrioventricular node-blocking drug should be instituted in patients treated with class Ic AADs (especially flecainide) to avoid transformation to AFL with 1:1 conduction.

48. AF ablation AF catheter ablation is effective in maintaining sinus rhythm in patients with paroxysmal and persistent AF. The main clinical benefit of AF catheter ablation is the reduction of arrhythmia-related symptoms. This has been confirmed in a recent RCT showing that the improvement in QoL was significantly higher in the ablation vs. medical therapy group as was the associated reduction in AF burden.

49. TRIAL STRATEGY JOURNAL N; DURATION RESULTS APAF STUDY C ircumferential P V A blation vs A ntiarrhythmic D rug T herapy for paroxysmal AF JACC, 2006 (ITALY) 99(CPVA) vs 99(ADT) 1 yr f/u AT free CPVA-86% vs ADT-22% (p<0.001) MANTRA PAF Catheter RFA vs Antiarrhythmic agents for paroxysmal AF NEJM, 2012 ( Multicetric RCT) 146(RFA) vs 148(AAT) 2 yr f/u Cumulative AF burden RFA-13% AAT-19% (p=0.10) PAROXYSMAL AF

50. TRIAL STRATEGY JOURNAL N; DURATION RESULTS CAMERA-MRI Study Catheter ablation vs Medical rate control AF with LV dysf (MR based) JACC, 2017 ( Multicentric RCT) 33 catheter ablation vs 33 medical rate control 6 mnth f/u EF normalised Catheter ablation grp - 58% Medical Tx - 9% (P-0.0002) { No LGE on MRI } CASTLE-AF Catheter ablation vs Medical therapy AF with HF (mean EF-32%) NEJM, 2018 ( Multicentric RCT) 179 Catheter ablation vs 189 Medical therapy Death & HF hospialization Catheter –28.5% Mx - 44.6% (p-0.006) AF WITH HF

51. TRIAL STRATEGY JOURNAL N; DURATION RESULTS CABANA TRIAL Catheter ablation vs Drug therapy JAMA, 2019 ( Multicentric RCT) 1108 catheter ablation vs 1096 Drug therapy 5 yrs f/u Primary end point Ablation-8% vs Drug- 9.2% (P = 0.30) CABANA Subgroup Catheter ablation vs Drug therapy AF with HF (EF<40%) N=778(35%) Primary end point  AF recurrence =CV mortality or HF hospi .

52. ‘C’ Cardiovascular risk factors and concomitant diseases: detection and management

53. Lifestyle interventions Obesity and weight loss Alcohol and caffeine use Physical activity Specific CV risk factors/comorbidities Hypertension Heart failure Coronary artery disease Diabetes mellitus Sleep apnoea

54. THANK YOU!