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Suvremena Terapija Atrijalne Fibrilacije K antonal na Bolnica Zenica. Enes Abdović. “ Atrial fibrillation (AF), an ‘old’ arrhythmia first described in 1909, ….

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atrial fibrillation af an old arrhythmia first described in 1909
“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”.
  • 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.
sex and age distribution of pts with af
Sex and Age Distribution of pts with AF

Abdovic et al. Europace 2005

etiological distribution of pts with af
Etiological distribution of pts with AF

Abdovic E. et al. Europace, 2005


Abdovic et al. Europace 2005

prevalence of af in several major chf trials
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.

the future of atrial fibrillation therapy the 2nd afnet ehra consensus conference
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
trigger factor
"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...
autonomic modulation preceding the onset of atrial fibrillation maisel et al jacc
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
vns af
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)
fibrosis is a hallmark of arrhythmogenic structural remodeling
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.

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
a proposed model for t he pathogenesis of af
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...

single multi level disease of the cardiac conduction system
 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


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.

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)

the future of antiarrhythmic therapy
… 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.
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.

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

new anticoagulants with mechanisms of action that are different from vitamin k antagonists
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.
Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group.

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.


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.


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.

Radiofrequency catheter ablation of AF by pulmonary vein isolation has emerged as an important treatment modality.
  • However, despite initial success, there is a substantial recurrence rate.
  • In a high percentage, the reason for recurrence is that pulmonary vein isolation is not complete due to local recovery of conduction out of the pulmonary veins. Re-ablation is then the method of choice.
  • In other cases, it might be important to change the underlying atrial substrate by identifying regions with continuous fractionated atrial electrograms which stand for regional fibrosis.
the outcome and complications of af ablation
… the outcome and complications of AF ablation.
  • The difficulty of evaluating AF ablation comes from the number of techniques used in ablation procedures.
  • All the series comparing ablation to pharmacological therapy have shown that the percentage of patients treated with ablation in sinus rhythm is superior (64 per cent) to medical therapy (26 per cent); in their series, 89 per cent versus 23 per cent.
  • The complications have an incidence which depends on the center and the experience of the operators. These complications concern the vascular access, the trans-septal puncture and the injury to the cardiac chambers. The risk of death during the procedure is reported to be around 0.1 per cent.

Schematic depiction of different ablation techniques targeting the lateralpulmonary veins (PVs).(A) Simultaneous isolation of the ipsilateral PVs by a long ‘‘pointby-point’’ lesion encircling the antrum area of the lateral PVs. (B) ‘‘Single shot’’ PV isolation using aballoon shaped catheter aiming at the LIPV.


… the statement of international societies concerning AF ablation and ablation guidelines cannot include class A recommendation as prospective comparative randomized trials are not available.

Registries such as the one conducted by Dr Cappato are useful but the long –term results are difficult to evaluate with a registry.

The CABANA trial will cover this gap and will randomize recent onset paroxysmal AF to antiarrhythmic medications or to ablation, which will include pulmonary vein isolation as a minimum procedure.

The primary endpoint will be mortality and secondary endpoints will include cardiovascular death, hospitalizations, heart failure, cost and quality of life.

conclusion 1
  • The classical risk factors for developing AF include HA, diabetes mellitus, valvular disease, ischaemic cardiomyopathy, CHF and thyroid disease.
  • HHD was by far the most prevalent associated medical condition.
  • Chronic AF was predominant in groups with advanced cardiac remodeling such as DCM and VHD.On the contrary to transient AF, it is a disease of the elderly.
conclusion 2
  • In order to prevent or postpone the development of AF an optimal treatment of hypertension and diabetes mellitus is necessery
  • early and comprehensive rhythm control therapy,
  • adequate control of ventricular rate and cardiac function,
  • continuous therapy to prevent AF-associated complications