Presentation is loading. Please wait.

Presentation is loading. Please wait.

Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments

Similar presentations

Presentation on theme: "Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments"— Presentation transcript:

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

2 Heart and ECG Normal electrical activation Left atrium Sinus node
Right atrium AV node ventricle Left atrium Conduction pathways Left Figure 1 The impulse then travels to the ventricles through conduction pathways made of specialized muscle fibers. The pathways divide into a network of smaller fibers which distribute the impulse throughout both ventricles. The impulse stimulates the ventricles, causing them to contract and pump blood. At rest, the sinus node normally initiates 60 to 80 beats a minute. With activity or excitement, the body requires greater blood circulation. A healthy sinus node responds to these changes in the body by increasing the heart rate accordingly.

3 Atrial tachycardia Sinus node AV node

4 Atrial Flutter Sinus node AV node

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

6 AF Prevalence by Age and Sex
Atrial Fibrillation: Prevalence Currently: millions people have AF in the USA In 2050: 7 – 15 millions people will have AF in the USA AF Prevalence by Age and Sex Age, y Prevalence of AF in a population of 1.89 million members of a large health maintenance organization in California. The error bars represent 95% confidence intervals. The numbers represent the number of men and women with AF in each age category. Go AS, et al. JAMA. 2001;285:

7 Atrial Fibrillation: Hospitalization

8 Atrial Fibrillation: Mortality

9 Atrial Fibrillation: Cost

10 Atrial Fibrillation vs. Ventricular Fibrillation
Ventricular fibrillation lasts for seconds or minutes in vivo. Kills within minutes. Atrial fibrillation can last for years Generally mild immediate consequences 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 Atrial fibrillation: Risk factors
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

14 Risk of atrial fibrillation.
The population-attributable risk of atrial fibrillation in men and women determined from a community-based longitudinal study.36 For both men and women, a substantial portion of atrial fibrillation risk remains unexplained. MI indicates myocardial infarction; HTN, hypertension; HF, heart failure; VHD, valvular heart disease; DM, diabetes mellitus; and LVH, ECG left ventricular hypertrophy. MI indicates myocardial infarction; HTN, hypertension; HF, heart failure; VHD, valvular heart disease; DM, diabetes mellitus; and LVH, ECG left ventricular hypertrophy. Benjamin et al . JAMA 1994

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

16 Cardiac Action Potential

17 Sinus node automaticity

18 Mechanisms of cardiac arrhythmias
Impulse formation:

19 Mechanisms of cardiac arrhythmias
Conduction disturbances: reentry

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

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

22 Masonic Medical Research Laboratory, Utica, NY
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: Atrial electrical and structural remodeling
Wijffels et al Circulation 1995

25 Constitutively Active (CA)
Atrial electrical remodeling (commonly due to AF) Normal Atria Remodeled Atria Ito1 ICa Ito1 IKur IKur Ito IKur ICa ICa IK1 IKr IKr IK-ACh (CA) IKs IKs IK1 IK1 INa INa IK-ACh, IK-ATP IK-ACh, IK-ATP Constitutively Active (CA)

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 Treatment of Atrial fibrillation
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

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 Surgery (Maze procedure): 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 Anticoagulation Risk of stroke in patients with atrial fibrillation
Score ≥ 2. Long term anti-coagulation is recommended

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

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

42 Several large clinical trials (i. e
Several large clinical trials (i.e., AFFIRM, RACE, PIAF, HOT CAFÉ, STAF, AF-CHF) have demonstrated that the rhythm control with anti-arrhythmic drugs is not superior to the rate control in terms of morbidity and mortality Adverse effects of drugs may balance or even exceed the beneficial effects. Several post-hoc or sub-study analyses of the large clinical trials (such as the DIAMOND, AFFIRM, CHF-STAF trials), directly comparing “sinus rhythm” vs. “AF” regardless of the initial rate or rhythm control assignment, indicate that AF patients maintained in sinus rhythm (with or without drugs) have better survival rate and better quality of life than those in whom AF persists

43 Treatment of Atrial fibrillation
Different types of information, gained from clinical assessment (upper left, turquoise), ECG (upper right, red), blood-based biomarkers (lower right, purple), and imaging (lower left, green) which may be useful to personalize AF management. The black boxes in the middle portion of the diagram illustrate different management domains which may be informed by different measures. 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

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

45 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: IKur IK-ACh CA IK-ACh INa (+IKr ?) “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 Treatment of Atrial fibrillation
Fuster et al Circ 2011 About 40% patients in whom AF first time detected will not develop AF within next 5 years.

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

50 Rhythm control: pharmacological approach


Download ppt "Atrial Fibrillation: Clinical Significance, Mechanisms, and Treatments"

Similar presentations

Ads by Google