Transcript Document

Suvremena Terapija Atrijalne
Fibrilacije
Kantonalna Bolnica Zenica
Enes Abdović
“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”.
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.
Sex and Age Distribution of pts with AF
250
Males
200
Females
150
100
50
0
16-20
21-25
26-30
31-35
36-40
41-45
46-50
51-55
56-60
61-65
66-70
71-75
76-80
Abdovic et al. Europace 2005
81-85
86-90
91-95 96-100
Etiological distribution of pts with AF
40%
35%
30%
25%
20%
37%
15%
23%
10%
18%
5%
14%
5%
3%
0%
HHD
DCM
CHD
VHD
Lone
Abdovic E. et al. Europace, 2005
Other
Results
Median age
71 years (16-100)
Male gender
51% (881)
Chronic AF
71% (1239)
Hypertension
67% (1167)
Diabetes mellitus
14.3% (249)
IV block
24% (421)
Thyroid gland diseases
5% (90)
Abdovic et al. Europace 2005
Transitory vs. Chronic AF
Transitory AF
Females
OR=1.28 95% CI=1.00-1.64
Younger pts
OR=1.04 95% CI=1.02-1.05
LoneAF
OR=3.85 95% CI=1.64-9.04
Hypertension
OR=1.47 95% CI=1.07-2.04
Chronic AF
Sex
Age
Concomitant/
Underlying
Disease
Males
Older pts
DCM
OR=2.19 95% CI=1.20-4.01
VHD
OR=4.27 95% CI=2.24-8.15
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.
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:
1.
2.
3.
4.
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
General schema representing AF
mechanisms and the role of
remodeling
"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
• 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
• 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
• 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.
Moe’s theory
the multiple reentry wavelet hypothesis
Moe 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
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
Sinus node

Sick sinus syndrome
(Intra, inter) atrial
level

Intra- and inter-atrial
blocks

Atrio-ventricular
blocks

Intra-ventricular
blocks
Atrio-ventricular level
Intra-ventricular level
Cardiac Conduction System
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 AF
Platonov PG, Cardiol J. 2008, 15;402-408
• Despite the advancements in pharmacological and nonpharmacological 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.
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.
• …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.
Advantages and disadvantages of “rate
control” and “rhythm control”
Angiotensin II Antagonist Prevents
Electrical Remodeling in Atrial Fibrillation
Nakashima 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.
Mechanism of Cardioembolic Ischemic
Stroke Caused by Atrial Fibrillation
Stroke risk in patients with AFaccording to the
CHADS2 risk index.
The colour coded bar graphs indicate the
appropriate antithrombotic treatment strategy.
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 Device
The 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 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.
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.
Overview of balloon based pulmonary vein
isolation techniques
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 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 transseptal 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
lateral pulmonary veins (PVs).
(A) Simultaneous isolation of the ipsilateral PVs by a long ‘‘pointbypoint’’ 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)
1. In order to prevent or postpone the
development of AF an optimal treatment
of hypertension and diabetes mellitus is
necessery
2. early and comprehensive rhythm control
therapy,
3. adequate control of ventricular rate and
cardiac function,
4. continuous therapy to prevent AFassociated complications