Suvremena Terapija Atrijalne Fibrilacije Kantonalna Bolnica Zenica

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Suvremena Terapija Atrijalne Fibrilacije
Kantonalna Bolnica Zenica

• Enes Abdovic

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Atrial fibrillation (AF), an old arrhythmia
first described in 1909,

• has assumed increasing importance in the 21st
  century, in which the global demographic tide has
  resulted in a rapidly expanding elderly
  population.
• AF is considered to be one of the three growing
  CV epidemics in the 21st century in conjunction
  with congestive heart failure (CHF), and type II
  diabetes mellitus, and/or metabolic syndrome.
  Moreover, AF and CHF frequently co-exist and each
  may exert an adverse prognostic impact upon the
  other.

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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.

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Sex and Age Distribution of pts with AF
Abdovic et al. Europace 2005
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Etiological distribution of pts with AF
Abdovic E. et al. Europace, 2005
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Results
Abdovic et al. Europace 2005
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Transitory vs. Chronic AF
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Prevalence of AF in several major CHF trials
The interrelations between AF and CHF could
constitute a vicious cycle. However, both
conditions may be markers of a common
pathophysiological substrate. According to data
from the Framingham Heart Study, AF preceded CHF
about as often as CHF preceded AF, and in
one-fifth of subjects, AF and CHF were diagnosed
for the first time on the same day.
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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

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

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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

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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)

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Fibrosis is a hallmark of arrhythmogenic
structural remodeling

• The fundamental mechanisms underlying AF have
  long been debated, but electrical, contractile,
  and structural remodeling are each important
  synergistic contributors to the AF substrate.
• In the dog model, atrial fibrosis causes
  localized regions of conduction slowing,
  increasing conduction heterogeneity and providing
  an AF substrate
• Fibrosis is a hallmark of arrhythmogenic
  structural remodeling. Tissue fibrosis results
  from an accumulation of fibrillar collagen
  deposits, occurring most commonly as a reparative
  process to replace degenerating myocardial
  parenchyma with concomitant reactive fibrosis,
  which causes interstitial expansion.

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Moes theory the multiple reentry wavelet
hypothesisMoe GK. On the multiple wavelet
hypothesis of atrial fibrillation.Arch Int
Pharmacodyn Ther 19621401838.

• ... 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

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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...

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Single/Multi Level Disease of the Cardiac
Conduction System

• ? Sick sinus syndrome

Sinus node (Intra, inter) atrial level
? Intra- and inter-atrial blocks
? Atrio-ventricular blocks
Atrio-ventricular level Intra-ventricular level
? Intra-ventricular blocks
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Cardiac Conduction System
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P-wave duration is generally accepted as the most
reliable non-invasive marker of atrial conduction
and its prolongation has been associated with
history of AFPlatonov PG, Cardiol J. 2008,
15402-408

• Despite the advancements in pharmacological and
  non-pharmacological management of atrial
  fibrillation (AF) observed during last decades,
  available treatment modalities and predictors of
  their success are still far from optimal.
• Understanding of pathophysiological mechanisms
  underlying AF and assessment of atrial
  electrophysiological properties using easily
  available non-invasive diagnostic tools such as
  surface ECG are essential for further improvement
  of patient-tailored treatment strategies.

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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)
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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.

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Advantages and disadvantages of rate control
and rhythm control
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Angiotensin II Antagonist Prevents Electrical
Remodeling in Atrial Fibrillation Nakashima H et
al. Circulation 20001012612.

• 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.

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Mechanism of Cardioembolic Ischemic Stroke Caused
by Atrial Fibrillation
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Stroke risk in patients with AFaccording to the
CHADS2 risk index. The colour coded bar graphs
indicate the appropriate antithrombotic treatment
strategy.
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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.

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Cumulative Hazard Rates for the Primary Outcome
of Stroke or Systemic Embolism, According to
Treatment Group.
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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.
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The Maze procedure Black 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.
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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. Numbers indicate the
distribution of foci in the pulmonary veins.
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Overview of balloon based pulmonary vein
isolation techniques
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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.

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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.

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Schematic depiction of different ablation
techniques targeting the lateral pulmonary 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.
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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.

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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.

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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