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Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments Alexander Burashnikov PhD, FHRS Cardiac Research Institute Masonic Medical Research.

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Presentation on theme: "Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments Alexander Burashnikov PhD, FHRS Cardiac Research Institute Masonic Medical Research."— Presentation transcript:

1 Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments Alexander Burashnikov PhD, FHRS Cardiac Research Institute Masonic Medical Research Laboratory Utica NY Campaign for Quality October 17-18, 2013

2 Sinus node Right atrium AV node Right ventricle Left atrium Conduction pathways Left ventricle Normal electrical activation Heart and ECG

3 Atrial tachycardia Sinus node AV node

4 Atrial Flutter AV node Sinus node

5 Atrial fibrillation (AF or AFib) AV node Sinus node

6 AF Prevalence by Age and Sex Go AS, et al. JAMA. 2001;285: Atrial Fibrillation: Prevalence Currently: millions people have AF in the USA In 2050: 7 – 15 millions people will have AF in the USA

7 Atrial Fibrillation: Hospitalization

8 Atrial Fibrillation: Mortality

9 Atrial Fibrillation: Cost

10 Atrial Fibrillation vs. Ventricular Fibrillation Atrial fibrillation can last for years Generally mild immediate consequences Ventricular fibrillation lasts for seconds or minutes in vivo. Kills within minutes. Atrial fibrillation can cause serious complications in a long ran: stroke tachycardia-mediated cardiomyopathy

11 Stroke 15-20% of all stroke in the United State is due to atrial fibrillation.

12 AF: tachycardia-mediated cardiomyopathy

13 Older than 60 years of age Diabetes High blood pressure Coronary artery disease Prior heart attacks Congestive heart failure Structural heart disease (valve problems or congenital defects) Prior open-heart surgery Untreated atrial flutter (another type of abnormal heart rhythm) Thyroid disease Chronic lung disease Sleep apnea Excessive alcohol or stimulant use Atrial fibrillation: Risk factors

14 Risk of atrial fibrillation. Benjamin et al. JAMA 1994 MI indicates myocardial infarction; HTN, hypertension; HF, heart failure; VHD, valvular heart disease; DM, diabetes mellitus; and LVH, ECG left ventricular hypertrophy.

15 Symptoms and Documentation of atrial fibrillation 15-30% of patients with AF are asymptomatic. Stroke is often the initial presenting sign of AF Shortness of breath Palpitations Chest pain Fatigue Reduced exercise capacity Dizziness, lightheadedness

16 Cardiac Action Potential

17 Sinus node automaticity

18 Mechanisms of cardiac arrhythmias Impulse formation:

19 Mechanisms of cardiac arrhythmias Conduction disturbances: reentry

20 Atrial fibrillation: Initiation and maintenance ECG Action potential Trigger (or extra-beat) Substrate (remodeling)

21 Mechanisms of maintenance of atrial fibrillation Nattel J Cardiovascular Research 54 (2002)

22 Gordon Moe, 1958, 1962, 1964 Masonic Medical Research Laboratory, Utica, NY The multiple Wavelet Hypothesis has been the dominating theory of cardiac fibrillation for several decades

23 Atrial fibrillation: Spatial and temporal electrical heterogeneity

24 AF begets AF: A trial electrical and structural remodeling Wijffels et al Circulation 1995

25 I to1 I Kur I Kr I Na I Ca I Ks I K-ACh, I K-ATP I K1 I to1 I Kur I Kr I Na I Ca I Ks I K-ACh, I K-ATP I K1 Constitutively Active (CA) I Ca I to I K1 I K-ACh (CA) I Kur Atrial electrical remodeling (commonly due to AF)

26 Atrial structural remodeling Can be due to: Rapid activation rate (AF) Hypertension Coronary artery disease Heart failure Age


28 Atrial fibrillation classification: Paroxysmal AF – self-terminating (< 7 days) Persistent AF – (> 7 days). Can be terminated (drugs, ablation or electrical cardioversion) Permanent AF – completely refractory to revision to sinus rhythm AF often progresses from short, rare episodes, to longer and more frequent attacks.

29 Rhythm or Rate control? Rhythm control: maintenance of sinus rhythm Rate control: control ventricular rate without making any specific attempts to suppress or prevent AF Anticoagulation (to prevent stroke): Commonly in both Treatment of Atrial fibrillation

30 Rhythm control: Restoration and maintenance of sinus rhythm. Pharmacological Catheter ablation Surgery Electrical cardioversion

31 Rhythm control: pharmacological Sodium channel blockers (propafenone, flecainide, etc): Potassium channel blockers (sotalol, dofetilide, ibutilide, etc): Multiple channel blockers (amiodarone, ranolazine, etc) Drugs prolong repolarization and depress excitability. AF Termination of AF

32 Pill-in-the-Pocket approach for termination of paroxysmal AF

33 Antiarrhythmic Drug Proarrhythmia: an Extension of Pharmacologic Effects Class IC toxicity: Atrial flutter with 1:1 AV conduction Class IA/III toxicity: Torsades de pointes

34 Rhythm control: catheter ablation

35 Left Atrial Catheter Ablation Pulmonary veins RF = radiofrequency. Oral H, et al. Circulation. 2003;108: Saad EB, et al. Circulation. 2003;108:

36 Rhythm control: Electrical cardioversion

37 Rate control Pharmacological: Depression of excitablilty of atrioventricular node (making ventricular rate < beats/min) Surgery (Maze procedure): Beta-blockers, calcium-channel blockers, digoxin

38 Rate control

39 Risk of stroke in patients with atrial fibrillation Score 2. Long term anti-coagulation is recommended Anticoagulation

40 Hart et al Ann Intern Med, 1999 Anticoagulation reduces stroke occurrence in patients with atrial fibrillation

41 Old and new anticoagulants Old Aspirin (often used with clopidogrel) Warfarin New: Dabigatran Rivaroxaban Apixaban


43 Kirchhof P et al. Europace 2013;europace.eut232 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author For permissions please Treatment of Atrial fibrillation

44 Current approach to stepwise decision making in patients with AF. Kirchhof P et al. Europace 2013;europace.eut232


46 Eur Heart J, 2013

47 Current investigational pharmacological strategies for AF treatment Atrial specific or selective therapy targets: I Kur I K-ACh CA I K-ACh I Na (+I Kr ?) Upstream therapy Targets: Structural remodeling Inflammation Oxidative stress Hypertrophy, Stretch, etc. Gap junction therapy targets: Cx40 Cx43 Normalization of intracellular calcium homeostasis Improvement of old agents: Amiodarone derivatives: Dronedarone Celivarone ATI-2042 Thank you

48 About 40% patients in whom AF first time detected will not develop AF within next 5 years. Treatment of Atrial fibrillation Fuster et al Circ 2011

49 Pro-arrhythmias in ventricles ! At slow heart rates and pauses, specific I Kr blockers predominantly prolong ventricular vs. atrial APD/ERP and induce EAD and TdP in ventricles not in atria.

50 Rhythm control: pharmacological approach


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