Suvremena Terapija Atrijalne Fibrilacije K antonal na Bolnica Zenica

1. Suvremena Terapija Atrijalne FibrilacijeKantonalnaBolnica Zenica Enes Abdović

3. “Atrial fibrillation (AF), an ‘old’ arrhythmia first describedin 1909,… • …has assumed increasing importance in the 21stcentury, in which the global demographic tide hasresulted in a rapidly expanding elderly population”. • “AF is considered to be one of the three growing CV epidemics in the 21st century in conjunctionwith congestive heart failure (CHF), and type IIdiabetes mellitus, and/or metabolic syndrome. Moreover,AF and CHF frequently co-exist and each mayexert an adverse prognostic impact upon the other”.

4. Background • Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in developed countries.  • It is a disease of the elderly and it is common in patients (pts) with organic heart disease. • Hypertension, DM, heart failure and valvular heart disease are predisposing factors to AF.

6. Sex and Age Distribution of pts with AF Abdovic et al. Europace 2005

8. Etiological distribution of pts with AF Abdovic E. et al. Europace, 2005

9. Results Abdovic et al. Europace 2005

11. Transitory vs. Chronic AF

13. Prevalence of AF in several major CHF trials The interrelations between AF and CHF could constitutea vicious cycle. However, both conditions may bemarkers of a common pathophysiological substrate. Accordingto data from the Framingham Heart Study, AF precededCHF about as often as CHF preceded AF, and in one-fifth of subjects, AF and CHF were diagnosed for the first time onthe same day.

14. The future of atrial fibrillation therapy: the 2nd AFNET/EHRA consensus conference: • Three main areas in need of research were identified: • Understanding the mechanisms of AF • Improving rhythm control monitoring and management • Validation and implementation of comprehensive cardiovascular risk management in AF patients • The expectation was that, in the future, adequate therapy for AF will need to simultaneously address: • management of underlying and concomitant diseases, • early and comprehensive rhythm control therapy, • adequate control of ventricular rate and cardiac function, • continuous therapy to prevent AF-associated complications

15. General schema representing AF mechanisms and the role of remodeling

16. "trigger" factor • In the presence of an opportunely modulated substrate, a prerequisite for the triggering of a multiple atrial reentry is the presence of an adequate "trigger" factor • This is represented, in most cases, by ectopic atrial beats, commonly originating in the pulmonary veins...

17. Autonomic modulation preceding the onset of atrial fibrillationMaisel et al. JACC • Among patients with structurally normal hearts, some have observed an increase in vagal predominance in the minutes preceding AF onset, while others have noted a marked shift towards sympathetic predominance • A number of other studies have also demonstrated that fluctuations in autonomic tone, as measured by HRV, precede the onset of AF • Acetylcholine shortens the atrial refractory period and increases the heterogeneity of atrial refractoriness, effects that predispose to reentry

18. vns - af • This survey shows that an autonomic trigger pattern for AF may be found in over 20% of patients. These patients are highly symptomatic explaining the more frequent application of rhythm control... • adrenergic (exercise, emotion, daytime only) • vagal (postprandial, sleep, night time only)

19. Fibrosis is a hallmark of arrhythmogenic structuralremodeling • The fundamentalmechanisms underlying AF have long been debated, butelectrical, contractile, and structural remodeling are eachimportant synergistic contributors to the AF substrate. • In the dog model,atrial fibrosis causes localized regions of conduction slowing,increasing conduction heterogeneity and providing an AFsubstrate • Fibrosis is a hallmark of arrhythmogenic structuralremodeling. Tissue fibrosis results from an accumulationof fibrillar collagen deposits, occurring most commonlyas a reparative process to replace degenerating myocardialparenchyma with concomitant reactive fibrosis, whichcauses interstitial expansion.

20. Moe’s theorythe multiple reentry wavelethypothesisMoe GK. On the multiple wavelet hypothesis of atrial fibrillation.Arch Int Pharmacodyn Ther 1962;140:183–8. • ... has served for nearly 50 years as a dominant conceptual model for explanation of the activation patterns and the maintenance of AF. • The hypothesis, initially demonstrated via computer modeling, found experimental and clinical support in humans with the therapeutic efficacy of the Maze procedure

21. A Proposed Model for the Pathogenesis of AF Experimental and clinical studies have shown that AF is maintained by multiple reentrant wavelets within the atrial muscle. It has been estimated that a critical number of wavelets (from 3 to 6) is necessary for perpetuation of AF...

23.  Sick sinus syndrome “Single/Multi Level Disease” of the Cardiac Conduction System Sinus node (Intra, inter) atrial level Intra- and inter-atrial blocks Atrio-ventricular blocks Atrio-ventricular level Intra-ventricular level Intra-ventricular blocks

24. Cardiac Conduction System

25. P-wave duration is generally accepted as the most reliablenon-invasive marker of atrial conduction and its prolongation has been associated with historyof AFPlatonov PG, Cardiol J. 2008, 15;402-408 • Despite the advancements in pharmacological and non-pharmacological management of atrialfibrillation (AF) observed during last decades, available treatment modalities and predictors oftheir success are still far from optimal. • Understanding of pathophysiological mechanismsunderlying AF and assessment of atrial electrophysiological properties using easily availablenon-invasive diagnostic tools such as surface ECG are essential for further improvement ofpatient-tailored treatment strategies.

28. Efficacy of amiodarone compared with control for the (A) prevention of sudden cardiac death, (B) cardiovascular death, and (C) all-cause mortality in patients with cardiomyopathy(Piccini JP et al, 2009 E Heart J)

29. … the future of antiarrhythmic therapy. • …classified the perspectives into 3 groups: • Atrial selective agents including vernakalant, amiodarone congeners and particularly dronedarone and others. • The latter group represents gap junction blockers, serotonin receptor antagonists and muscarinic receptor blockers. • Does dronedarone represent a progress in terms of efficacy and safety? Yes referring to the recent results of the ATHENA trial, which showed that dronedarone decreased cardiovascular hospitalisation by 26 per cent, the first AF related hospitalisation by 46 per cent, all AF related hospitalisation by 23per cent and reduction of the number of days of hospitalisation. This multichannel blocker without iodine is the first antiarrhythmic agent which reduced cardiovascular events and cardiovascular mortality.

30. Advantages and disadvantages of “rate control” and “rhythm control”

35. Angiotensin II Antagonist Prevents Electrical Remodeling in AtrialFibrillationNakashima H et al.Circulation 2000;101:2612. • The inhibition of endogenous Ang II prevented AERP shortening during rapid atrial pacing. • These results indicate for the first time that Ang II may be involved in the mechanism of atrial electrical remodeling and that the blockade of Ang II may lead to the better therapeutic management of human atrial fibrillation.

43. Mechanism of Cardioembolic Ischemic Stroke Caused by Atrial Fibrillation

45. Stroke risk in patients with AFaccording to the CHADS2 risk index.The colour codedbar graphs indicate the appropriate antithrombotictreatment strategy.

46. New anticoagulants with mechanisms of action that are different from vitamin K antagonists… • … the novel factor IIa and Xa antagonists like dabigatran and rivaroxaban, their mechanism of action and presently available results. • In patients with atrial fibrillation, dabigatran 110 mg was associated with similar rates of stroke and systemic embolism to warfarin, and lower rates of major hemorrhage. Dabigatran 150 mg was associated with lower rates of stroke and systemic embolism than warfarin, and similar rates of major hemorrhage.

47. Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group.

48. The Watchman Left Atrial Appendage Closure DeviceThe device is a self-expanding nitinol structure that is delivered percutaneously with femoral venous access and transseptal technique to the LAA. The device is positioned with the use of angiography and TEE, and implantation is performed in either a cardiac catheterization or electrophysiology laboratory with the patient under general anesthesia or conscious sedation.

49. The Maze procedureBlack lines delineate surgical incisions in both the right and left atria, encircling the pulmonary veins (PV) and around the coronary artery sinus orifice. The atrial appendages are also excluded.

50. Diagram of the Sites of 69 Foci Triggering Atrial Fibrillation in 45 Patients.Note the clustering in the pulmonary veins, particularly in both superior pulmonary veins. Numbersindicate the distribution of foci in the pulmonary veins.