Download fibrillation atriale : strategie antiarythmique, cardioversion

FIBRILLATION ATRIALE :
STRATEGIE ANTIARYTHMIQUE, CARDIOVERSION
(PHARMACOLOGIQUE ET ELECTRIQUE)!
J.Y. LE HEUZEY!
Hopital Georges Pompidou!
Université René Descartes, Paris!
DIU Rythmologie / Stimulation, 29 Janvier 2014!
Projected number of adults with AF in the US over the period 1995-2050 "
a 2.5-fold increase
N=756 patients with one ECG-AF episode or more at baseline
(PAF, n = 167 ; Chronic, n = 389 ; Recent Onset, n = 200)
Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm
management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5.
Total cost :
3209 € per year
FR = 2.5 Billion €
EU = 25 Billion €
THE COCAF STUDY
DISTRIBUTION OF COSTS
Hospitalisations
"
2%
8%
9%
6%
Drugs
Consultations
Further
investigations
23 %
Paramedical
procedures
Loss of work
Le Heuzey et al., !
Am. Heart J. !
2004, 147 : 121-6!
H
E
G
P
52 %
ATRIAL FIBRILLATION : WHICH TREATMENT ?
I- PHARMACOLOGICAL THERAPY!
•  Antithrombo-embolic therapy : !
•  vitamine K antagonists!
•  antiplatelet drugs!
•  heparin (s)!
•  direct oral anticoagulants (antithrombin and antiXa) !
!
•  Antiarrhythmic therapy : !
•  in cardioversion (pharmacological cardioversion or
preparation to electrical cardioversion)!
•  in maintenance of sinus rhythm!
•  in rate control!
H
E
G
P
ATRIAL FIBRILLATION : WHICH TREATMENT ?
II- NON PHARMACOLOGICAL THERAPY!
•  Occluders!
•  Electrical cardioversion!
•  Ablation :!
•  pulmonary vein isolation (+ atrial lines, defragmentation …)!
•  A-V node (+ pacing)!
•  Pacing (bi-atrial, specific algorithms)!
•  Surgery (maze, thoracoscopy …)!
!
H
E
G
P
CLASS I ANTI-ARRHYTHMIC DRUGS
IN DEVELOPMENT (1984)!
""
"
"
• Encainide
• Penticainide
• Indocainide
• Lorcainide
• Mesocainide
• Recainam
• Moricizine
• Carocainide
• Diprafenone
• Pirmenol
• Tocainide
• Nicainoprolol
Odds Ratio/Total mortality patients treated
with quinidine /Control
RCT
n
Boissel
Byrne-Quinn
212
92
Hartel
175
Hillestad
100
53
Lloyd
Sodermark
176
ALL STUDIES N = 808
0
1
Quinidine better
Coplen SE. Circulation. 1990;82:1106-1116.
2
3
4
5
6
7
8
9
10 11 12
Quinidine worse
Odds Ratio (Quinidine: Control)
After CAST, Coplen(quinidine meta
analysis), SWORD, SPAF (Flaker), …
AFFIRM ...
•  The main goal is a good safety (i.e. a lower
risk)"
•  Nevertheless we need AA drugs to treat
patients with underlying cardiopathies
(CAD, HF… )"
… and the risk is higher in these patients
VAUGHAN – WILLIAMS
CLASSIFICATION !
-  Class I : sodium inhibitors!
!
•  Ia : Quinidine, Disopyramide!
•  Ib : Lidocaïne, Mexiletine!
•  Ic : Flecaïnide, Propafenone, Cibenzoline!
-  Class II : beta-blockers!
-  Class III : potassium blockers : Amiodarone, Sotalol!
-  Class IV : calcium inhibitors : Verapamil, Diltiazem!
GAMBIT, n. Chess : !
!(it. Gambetto, trip) !
!
a chess move early in the game in which the player
s a c r i fi c e s p i e c e s i n o r d e r t o o b t a i n a n
advantageous position!
Primary end point : total mortality (all causes) !
25"
“Rate”"
Mortality (%)"
20"
“Rhythm”"
p = 0.078"
15"
10"
5"
0"
0"
"“Rate” n : !2027,0
"“Rhythm” n : !2033,0
AFFIRM
1"
!1926,78
!1932,80
2"
!1827,148
!1807,175
Atrial Fibrillation Follow-up Investigation of Rhythm Management
H
E
G
P
3"
!1329,210
!1316,257
4"
!774,275
!780,314
5"
!236,306!
!255,352!
Time
(years)!
RACE study: composite end point!
(cardiovascular mortality + thromboembolic complications + bleeding + implantation of a pacemaker + heart failure
+ severe adverse events of antiarrhythmic drugs)!
Van Gelder IC, et al. N Engl J Med 2002;347:1834-40.
D. Roy et al., New Engl. J. Med. 2008; 358 : 2667 - 77!
RHYTHM OR RATE CONTROL ?!
§  Rhythm control better choice for :
!younger patients, highly symptomatic
!patients or patients with few risk factors of
!relapse!
§  Rate control better choice for:
!older patients, asymptomatic patients or !
!patients with few symptoms, patients with
!advanced underlying heart disease!
H
E
G
P
Relationships between sinus rhythm, treatment, and survival in the
Atrial Fibrillation Follow-up Investigation of Rhythm Management
(AFFIRM) study!
!
!
The AFFIRM investigators, Circulation 2004; 109 : 1509-1513!
H
E
G
P
20
RACE II
Van Gelder I. et al, NEJM 2010, 362 : 1363 - 73
14.9
15
12.9
Strict control
10
Lenient control
5
0
0
6
12
18
24
30
36
246
255
212
218
131
138
),
!",*
Strict control
Lenient control
303
311
282
298
273
290
262
285
Choice of Strategy at Baseline by
Cardiologists
n=5604
Rate control strategy
Rhythm control strategy
n=2528
45.1%
n=3076
54.9%
0
10
20
30
40
50
Le Heuzey J.Y. et al. Am.J. Cardiol. 2010; 105 : 687 - 93
60
%
Baseline Demographics and Comorbidities
Mean age years (SD)
Female
Resting heart rate
n=5604
n=3076
n=2528
n=5604
64.2 (12.0)
43%
76.6 bpm
67.3 (11.6)
43%
80.6 bpm
65.6 (11.9) p<0.001
43%
78.4 bpm p<0.001
Ethnicity Caucasian
81
9
9
8
History of Myocardial
Infarction
Valvular Heart Disease
19
16
16
17
15
History Diabetes
p<0.001
24
10
LVEF <40%
7
History Heart Failure
23
22
24
20
HF NYHA I + II
Rhythm-control
p<0.001
26
30
p<0.001
p<0.001
68
69
68
History HTN
8
9
7
History Stroke/TIA
History CAD
Fam. hist. Premature CV
Disease
Lone AF
0
18
20
18
20
20
21
19
16
21
20
p<0.001
Rate-control
42
41
43
13
90
Total
p=0.006
History Dyslipidemia
86
%
p<0.001
40
60
80
*p value compares the percentage of the condition between rhythm control vs. rate control
Le Heuzey J.Y. et al. Am.J. Cardiol. 2010; 105 : 687 - 93
100
Clinical Presentation of AF at Baseline
Rhythm-control
Rate-control
Total
n=5604
p< 0.001*
57
Atrial fibrillation at
inclusion
81
39
Sinus rhythm
at inclusion
43
20
63
76
Symptomatic
19
Asymptomatic
15
48
66
32
34
0
85
24
AF persistent
AF paroxysmal
81
20
40
52
68
60
80
100
*p value <0.001 for all comparisons
Le Heuzey J.Y. et al. Am.J. Cardiol. 2010; 105 : 687 - 93
%
Origin of atrial premature beats!
Right Atrium!
!
Superior!
vena cava
Left Atrium
Septum
17
Fossa
ovalis
!
Inferior!
vena cava
!
!
!
31
!
Pulmonary
veins
6
11
Coronary
sinus!
"
Haissaguerre M et al.
N. Engl. J. Med. 1998; 339 : 659 - 66!
H
E
G
P
THE A4 STUDY
Jais P. et al. Circulation 2008; 118 : 2498 - 2505!
and require a higher number of procedures (11,12), type of
Vol. 57, No. 2, 2011
AF was not a predictor of
outcome in the multivariate
ISSN 0735-1097/$36.00
doi:10.1016/j.jacc.2010.05.061
Herein, we report the longest follow-up to date of any
analysis.
percutaneous AF procedure. By 5 years of follow-up,
Importantly, ourHeart
study
population
Rhythm
Disorderswas not representative
freedom from recurrent AF was 63%, albeit with repeat
of patients with AF at large, as it consisted predominantly of
interventions in 51%. Catheter
Moreover, Ablation
we observed
gradualFibrillation
younger, healthier, nonobese patients with relatively smaller
for aAtrial
attrition in arrhythmia-free survival, with an 8.9% annual
atria and paroxysmal or recent progression to persistent AF.
recurrence rate following
last ablation
attempt.
Notably,
Electrophysiological mechanisms underlying early recurArethe
Results
Maintained
at 5 Years
of Follow-Up?
the long-term effectiveness of a single procedure was modrences following PV isolation have been extensively studied.
Rukshen Weerasooriya, BMEDSC(HONS), MBBS,*† Paul Khairy, MD, PHD,‡ Jean Litalien, MD,*
est, with 29% arrhythmia-free survival at 5 years. No new or
In recurrences #3 months after ablation, Gerstenfeld et al.
Laurent Macle, MD,‡ Meleze Hocini, MD,* Frederic Sacher, MD,* Nicolas Lellouche, MD,*
unforeseen sequelae of
catheter ablation were detected
(13) found that 61% of PVs had recovered conduction.
Sebastien Knecht, MD,* Matthew Wright, PHD, MD,* Isabelle Nault, MD,* Shinsuke Miyazaki, MD,*
beyond periprocedural Christophe
complications,
withJacques
no thromboemCallans
et al. (14)
reconnection accounted
Scavee, MD,*
Clementy, MD,* Michel
Haissaguerre,
MD,*reported
Pierre Jais, that
MD* PVJACC
164
Weerasooriya et al.
Vol. 57, No. 2, 2011
bolic Atrial
events
or
clinically
significant
PV
stenosis.
These
for
77%
of
recurrences.
Extending
the
follow-up to 12
Bordeaux-Pessac,
France; Crawley, Western Australia; and Montreal, Quebec, Canada
Fibrillation Ablation:
5-Year Follow-Up
January 11, 2011:160–6
results have implications for the long-term follow-up of
months, Mainigi et al. (15) found that 75% of implicated
patients after radiofrequency
catheter This
ablation
for5-year
AF.
Objectives
study describes
follow-up results of catheter ablation for atrial fibrillation (AF).
dures become more widely performed and increasingly
The long-term success Background
rates in ourLong-term
studyefficacy
arefollowing
consistent
catheter ablation of AF remains unknown.
influence overall health care expenditure. Although prior
with prior reports of 70%Methods
at 20 months
and
66%
at 14
26women), age 55.7 ! 9.6 years, referred to our center for a first AF ablation
A total(5)
of 100
patients
(86 men,
studies
have concluded
that
net benefit
of catheter
paroxysmal; 3.5 ! 1.4 prior ineffective
antiarrhythmic
agents) were followed
for 5 the
years. Complete
sucmonths (6) and an 8.7% long-term (63%
recurrence
rate at 28
cess was defined as absence of any AF or atrial tachycardia recurrence (clinical or by 24-h Holter monitoring)
ablation over medical therapy extends to approximately
s.
months described by Shah et al. (7).lasting
In !30
further
extending
5 years (8,9), projected costs have not considered later (i.e.,
survival
rates after
the follow-up period, we Results
noted that Arrhythmia-free
the rate of
decline
ina single catheter ablation procedure were 40%, 37%, and 29% at 1, 2,
years)
and reinterventions.
and 5 years, respectively, with most"3
recurrences
over recurrences
the first 6 months. Patients
with long-standing persis- For example,
freedom from AF after the first intervention
stabilized
tent AF experienced
a higher after
recurrence rate than those with paroxysmal or persistent forms (hazard ratio
Khaykin et al. (9) assumed a maximum 5% late recurrence
1.9, entirely
95% confidence
interval [CI]: 1.0 to 3.5; p " 0.0462). In all, 175 procedures were performed,
the initial 12 months, although it did[HR]:
not
plateau.
with a median of 2 per patient. Arrhythmia-free
survival following
the last catheter results
ablation procedure
rate, which
underestimates
fromwasour long-term
Clinical implications of these results87%,
are81%,substantial
and 63% at 1, 2, with
and 5 years, respectively. Valvular heart disease (HR: 6.0, 95% CI: 2.0 to 17.6;
findings. Given
that
in pthis
study
p " 0.0012) and nonischemic dilated
(HR: 34.0,
95%patients
CI: 6.3 to 182.1;
# 0.0001)
inde- were relatively
regard to the care of patients with AF.
Firstly, empirical cardiomyopathy
pendently predicted recurrences. Major
complications
(cardiac
tamponade
requiring
drainage)
occurred
in
young, with an average age of 55 years at entry,
extending
long-term follow-up data should be presented
to patients to
3 patients (3%).
follow-up even further would be of interest in determining
inform the decision-making
process and
provide
Conclusions
In selected
patients reasonable
with AF, a catheter ablation strategy with repeat intervention as necessary provides acceptlikelihood
oftheAF
over
a lifespan.
able long-term relief. Although most the
recurrences
transpire over
first 6recurrence
to 12 months, a slow
but steady
deexpectations. Secondly, ongoing surveillance
is
warranted,
cline in arrhythmia-free survival is noted Patients
thereafter. (J had
Am Coll a
Cardiol
2011;57:160–6)
©
2011
by
the
median of 2.0 procedures, reflecting a
College
of Cardiology Foundation
even if catheter ablation was deemed American
initially
successful.
In
treatment strategy favoring early reintervention for recuraccordance with the recently published consensus statement
rences (10). The high rate of repeat procedures accounts, in
(1), patients with aCatheter
previous
history
of
stroke
should
not
ablation that predominantly targets pulmonary
Because
theMultiple
substrate
for AFbetween
may Success
evolveevent-free
in a
part,years.
for
the 3marked
disparity
survival
Figure
Procedure
Figure
2 Single
Procedure
Success
discontinue
anticoagulation
veins (PVs) therapy.
is well established as a treatment option for
time-dependent fashion, the critically important question
rates following
singleablation
and final
patients with symptomatic drug refractory atrial fibrillation
as to whether
simplyinterventions.
slows disease pro-The benefit of
Late recurrences and
frequent reinterventions should also arisesKaplan-Meier
event-free survival curve after the last catheter ablation attempt.
Kaplan-Meier event-free survival curve after a single catheter ablation attempt.
Discussion
Journal of the American College of Cardiology
© 2011 by the American College of Cardiology Foundation
Published by Elsevier Inc.
CABANA Pilot Study
Recurrence of Any AF, AFL, or AT"
AF/AFL/AT recurrence (%)
1,0
QuickTime™ and a
decompressor
ar e neede d to see this picture.
HR 0.69 (0.37-1.32) P=0.264
Drug
(72)
0,8
(59)
0,6
66%
Blanking
period
Ablation
(50)
0,4
72%
(36)
0,2
0,0
0
Ablation Rx
Drug Rx
29
31
CABANA Pilot Study; ACC 2010
3
26
30
6
9
Time (months)
18
12
14
8
12
4
5
3033548-
… so what ?!
Number of
patients
600,000!
Number of
cardiologists
5,000!
Centers
performing AF
ablation 20!
Maximum*
number of
patients / year
15,600!
Courtesy C. de Chillou!
2.6% !
*
3 patients / day per
center = 12h / day!
Amiodarone!
BENZOFURANES
Amiodarone
Dronedarone
Budiodarone
Celivarone
Dronedarone!
Dronedarone Significantly Decreased Risk of CV
Hospitalisation or Death by 24%
Cumulative Incidence (%)
50
Placebo on top of standard therapy*
DR 400mg bid on top of standard therapy*
24% reduction
in relative
risk
40
30
20
HR=0.76
p<0.001
10
Months
0
0
6
12
18
24
30
Patients at risk:
Placebo
2327
1858
1625
1072
385
3
DR 400mg bid
2301
1963
1776
1177
403
2
* Standard therapy may have included rate control agents (beta-blockers, and/or Ca-antagonist and/or digoxin) and/or anti-thrombotic therapy (Vit. K antagonists
and /or aspirin and other antiplatelets therapy) and/or other cardiovascular agents such as ACEIs/ARBs and statins.
Mean follow-up 21 ±5 months.
Hohnloser SH et al. N Engl J Med 2009;360:668-78.
30
DIONYSOS
Primary Endpoint: More AF Events But Less Early
Discontinuation With Dronedarone
Cumulative incidence
1.0
0.8
184 (73.9%)
43 endpoints
0.6
141 (55.3%)
42 endpoints
0.4
RRR (95%CI) = 1.589 (1.275;1.98)
0.2
p-value <0.001
0.0
0
3
6
9
12
Patients at risk
15
Months
249
99
84
40
12
0
255
146
126
61
13
0
Number of patients with endpoint
ECG documented AF endpoint
Documented AF after conversion
Unsucessful electrical cardioversion
No spontaneous conversion and no electrical cardioversion
on day 10 to day 28
Premature study drug discontinuation
Lack of efficacy
Intolerance
Dronedarone
Amiodarone
Dronedarone
Amiodarone
(n=249)
(n=255)
184 (73.9%)
158 (63.5%)
141 (55.3%)
107 (42.0%)
91 (36.5%)
29 (11.6%)
62 (24.3%)
16 (6.3%)
38 (15.3%)
29 (11.4%)
26 (10.4%)
34 (13.3%)
1 (0.4%)
25 (10.0%)
0
34 (13.3%)
Le Heuzey J.Y. et al., J. Cardiovasc. Electrophysiol. 2010; 21 : 597 - 605
Stroke, systemic embolism, myocardial
infarction or cardiovascular death
First Co-primary
Outcome
Dronedarone
Placebo
Dronedarone vs placebo
HR and 95% CI
43 (2.7%)
19 (1.2%)
2.29 (1.34 – 3.94) p=0.002
0.05
Dronedarone
0.04
Placebo
0.03
0.02
Cumulative Incidence
0.01
Days
0.00
Number
at risk :
0
30
60
90
120
150
180
Dronedarone
1619
1421
930
353
Placebo
1617
1445
908
377
AF may emerge along the CV continuum and is a
contributing factor in many CV conditions
Remodeling
MI
HF
End-stage
microvascular
heart disease
Atherosclerosis and
LVH
Risk factors
(diabetes,
hypertension)
Ventricular
dilation
Atrial fibrillation
Death
33
Fuster V, et al. Europace 2006;8:651-745.
European Heart Journal
http://eurheartj.oxfordjournals.org/
Eur. Heart J. 2010; 31 : 2369 - 429
www.escardio.org
ESC GUIDELINES
European Heart Journal (2012) ...
doi:10.1093/eurheartj/..
2012 Focused Update of the ESC Guidelines for
the Management of Atrial Fibrillation
An update of the 2010 ESC Guidelines for the Management of Atrial Fibrillation
Developed with the special contribution of the European Heart Rhythm Association
Authors/Task Force Members: A. John Camm (Chairperson) (UK)*, Dan Atar (Norway), Raffaele de
Caterina (Italy), Gerhard Hindricks (Germany), Stephan H. Hohnloser (Germany), Paulus Kirchhof
(Germany/UK), Gregory Y. H. Lip (UK), Irene Savelieva (UK)
ESC Committee for Practice Guidelines (CPG): Jeroen J. Bax (CPG Chairperson) (The Netherlands),
Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK),
Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (The
Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa
McDonagh (UK), Cyril Moulin (France), Bogdan A. Popescu (Romania), Željko Reiner (Croatia), Udo Sechtem
(Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian
(France),Stephan Windecker (Switzerland).
Document Reviewers: Panos Vardas (Review Coordinator) (Greece), Nawwar Al-Attar (France), Ottavio Alfieri †
(Italy), Annalisa Angelini (Italy), Carina Blomstrom-Lundqvist (Sweden), Paolo Colonna (Italy), Johan de Sutter
(Belgium), Sabine Ernst (UK), Andreas Goette (Germany), Bulent Gorenek (Turkey), Robert Hatala (Slovak
Republic), Hein Heidbuchel (Belgium), Magnus Heldal (Norway), Steen Dalby Kristensen (Denmark), Philippe
Kolh† (Belgium), Jean-Yves Le Heuzey (France), Iraklis Mavrakis (Greece), Lluis Mont (Spain), Pasquale Perrone
Filardi (Italy), Piotr Ponikowsky (Poland), Bernard Prendergast (UK), Frans Rutten (The Netherlands), Ulrich
Schotten (The Netherlands), Isabelle C. Van Gelder (The Netherlands), Freek Verheugt (The Netherlands)
The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
Keywords:
Atrial fibrillation, European Society of Cardiology, Guidelines, Anticoagulation, Rate control,
Rhythm control, Upstream therapy, Pulmonary vein isolation, Left atrial ablation
Eur. Heart J. 2012; 33 : 2719 - 47!
www.escardio.org
* Corresponding authors: A. John Camm, Division of Clinical Sciences, St.George's University of London, Cranmer Terrace,
Tooting, London SW17 0RE, United Kingdom – Tel.: +44 20 8725 3414 - Fax: +44 20 8725 3416 - Email: [email protected]
Recommendations
Total = 210
Class of Recommendation
www.escardio.org
Level of Evidence
www.escardio.org
www.escardio.org
Eur. Heart J. 2010, 31 : 2369 - 469
Page 20 of 29
ESC Guidelines
Significant structural heart disease
Minimal or no structural
heart disease
Treatment of underlying condition and prevention
of remodelling – ACEI/ARB/statin
HHD
No LVH
dronedarone/flecainide/
propafenone/sotalol
CHD
LVH
sotalol
dronedarone
dronedarone
amiodarone
amiodarone
HF
amiodarone
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; HHD = hypertensive heart disease; CHD = coronary heart disease; HF = heart failure;
LVH = left ventricular hypertrophy, NYHA = New York Heart Association. Antiarrhythmic agents are listed in alphabetical order within each treatment box.
Figure 4 Choice of antiarrhythmic drug according to underlying pathology.
dysfunction. For patients in NYHA functional class III or IV, there is
evidence from the ANDROMEDA (ANtiarrhythmic trial with
DROnedarone in Moderate-to-severe congestive heart failure
www.escardio.org
Evaluating
morbidity DecreAse (ANDROMEDA) trial that these
patients may derive harm from dronedarone therapy.149 On the
adverse event reporting. Therefore, it seems unnecessary to
remove this option for the treatment of hypertension with left ventricular hypertrophy, where the risk from antiarrhythmic drugs is
thought to be related to torsades de pointes.
ESC GUIDELINES 2012 UPDATE!
Original Article
Amiodarone and the Risk of Cancer
Amiodarone and the Risk of Cancer/Su et al
A Nationwide
Population-Based Study
Risk Factors for Cancer in Patients
1
2,3,4
; Kun-Ta Chou, MD1,3; Shuo-Ming Ou, MD5; Yu-Chin Lee, PhD1,3;
Amiodarone Vincent Yi-Fong Su, MD ; Yu-Wen Hu, MD
Elizabeth Ya-Hsuan
Lin, BSc6; Tzeng-Ji Chen, PhD3,7; Cheng-Hwai Tzeng, PhD3,8; and Chia-Jen Liu, MD3,4,8,9
Multivariate
Univariate
Analysis
Analysisa
InHR
postmarketing
HR BACKGROUND:
(95% CI)
P
(95% CI)
P surveillance, the US Food and Drug Administration has reported the development of lung masses,
thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database,
us
1.04
1.98
1.11
3.81
1.15
1.04
(1.03-1.06)
<.001
1.04 (1.03-1.06)
<.001
the authors
conducted
a population-based
cohort study. Patients who were treated with amiodarone between 1997 and 2008 were
(1.45-2.72)
<.001 1.90 (1.38-2.62)
<.001
enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare
(0.81-1.51)
.524
the cancer<.001
incidence
of the study
(2.16-6.69)
3.70 (2.10-6.52)
<.001 cohort with that of the general population. A multivariate Cox regression model was used to
evaluate the
association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study
(0.85-1.56)
.364
(0.69-1.55)
.856 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased
included 6418
with borderline
significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [P ¼ .067]). Male patients had a higher risk
.807
95%
.180 CI, 1.02-1.36 [P ¼ .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were
.961 SIRs of 1.28 (95% CI, 1.00-1.61; P ¼ .046) and 1.46 (95% CI, 1.11-1.89; P ¼ .008), respectively. After adjustment for
have
age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P ¼ .006) for the high tertile of cDDDs compared with the
m
0.25 (0.06-0.99)
.048
0.33 (0.08-1.35)
.123
Figure 1. On Kaplan-Meier analysis excluding the person-time
low tertile..328
CONCLUSIONS: The resultsand
of events
the current
indicate
that
may be associated with an increased
0.05 (0.00-20.57)
occurringstudy
within the
first year,
theamiodarone
cumulative inciC 2013 American Cancer Society.
e, NTD)c risk of incident cancer, especially in males,
V
dence
patients with low,
intermediate,
high numbers
withamong
a dose-dependent
effect.
Cancerand
2013;119:1699–705.
9
0.96 (0.72-1.30)
(SIR, 1.18;
1.24 (0.91-1.69)
0.99 (0.74-1.33)
found to
of cumulative defined daily doses (cDDDs) (! 103, 103-253, and
0.51 (0.37-0.70)
<.001 0.63 (0.45-0.87)
.006
> 253) thyroid
of amiodarone
was
found
to differ significantly (log-rank
0.52 (0.34-0.78)
.002amiodarone,
0.62 (0.41-0.94)
.024malignancy,
KEYWORDS:
cancer,
cancer,
lung
cancer.
0.77 (0.50-1.18)
.227
0.75 (0.51-1.12)
.160
1.001 (1.000-1.002) .008
P ¼ .023).
1.001 (1.000-1.002) .022
INTRODUCTION
DISCUSSION
Amiodarone,
which
was
approved
by
thethe
USbest
Food
and
Drug Administration
To
of our
knowledge,
the current study isfor
thethe
first treatment of arrhythmias in 1985, is
95% CI, 95% confidence interval; cDDD, cumulative
N=141500
www.escardio.org
Andersen S. et al Europace 2009; 11 : 886 - 91
DC shock delivered for first time in 1947 to treat a VF, routinely
used to treat AF since 1967 (Lown)
RECOMMENDATIONS!
FOR!
DIRECT CURRENT!
CARDIOVERSION!
www.escardio.org
DCC : When ?
www.escardio.org
ORGANIZATION AND TECHNICAL ASPECTS !
Ø Anesthetist assessment before cardioversion
Ø Digoxin, K+, INR, … before cardioversion
Ø Fasting and steady state, perfused, reanimation room
Ø Short duration anesthesia (Propofol, 1cc/10Kg)
Ø Adhesive + gelled electrodes +++
Ø Rhythm, arterial pressure, O² saturation, permanent
monitoring, up to 3 h after the shock
Adapted from S. Boveda
- Electrodes diameter (inverse relationship between
surface and impedance/current density) : 8 to 12 cm
- Electrode / skin interface : gelled electrodes
- Anteroposterior positioning : 2nd et 3rd right
intercostal spaces / left scapula angulus : 50% less
energy (Lown,1964)
- Avoid sternum and vertebrae (high impedance) : 96%
of energy delivered away from the heart
- 3 biphasic shocks (if necessary) for every session
- First shock delivered at 100 J if normal weighted
patient and AF < 1 year, then increase energy until
200 J
Adapted from S. Boveda
Cardioversion in patients with pacemakers and ICDs
Ø  The electrode paddle at least 8 cm from the battery,
and the anteroposterior positioning is recommended
Ø  Biphasic shocks are preferred because they require
less energy for AF termination
Ø  In pacemaker-dependent patients, an increase in
pacing threshold should be anticipated
Ø  After cardioversion, the device should be
interrogated and evaluated to ensure normal function
Adapted from S. Boveda
« biphasic shock has greater efficacy,
requires fewer shocks and lower
delivered energy, than a monophasic
shock » R. Page, JACC 2002
S Mittal, Circulation 2000
CEE – Electrodes Positioning
« The anteroposterior
(right anterior, left
posterior) defibrillator
paddle position is superior
to the anterolateral
location »
GL Botto, Heart 1999
DCC / Primary Success Rate Factors
GL Botto, Heart 1999
DCC : COMPLICATIONS
Ø Stroke risk if poor anticoagulation (1 to 7%)
Ø VF if wrong R wave synchonization, hypoK+, digitalic
overload, or myocardial ischaemia...
Ø Beware of refractory VF if digitalic overload+++
Ø Bradycardia if SSS or AV block (be careful if slow AF
or AAD associations…)
Ø Myocardial injury : high energy iterative shocks (>400
Joules) and small diameter electrodes (Warnes, 1975)
Ø Pacemaker or ICD dysfunction
Adapted from S. Boveda
DCC : Take Home Message
Ø DCC : effective, safe and easy-to-do AF treatment
Ø Very low risk of complications if guidelines are respected
Ø Ambulatory feasibility
Ø 3 hours post cardioversion monitoring
Ø Higher success rate when cardioversion is done early
Ø AAD in order to enhance DCC and prevent recurrences…
Ø OAC at least 3 weeks after cardioversion, depending on CHA²DS²VASc score…
Ø AF recurrence risk : remains 50% at 1 year…
Courtesy S. Boveda
RECOMMENDATIONS!
FOR!
PHARMACOLOGICAL!
CARDIOVERSION!
www.escardio.org
H
E
G
P
Flecainide or Propafenone « pill in the pocket »!
H
E
G
P
ATRIAL REPOLARIZATION
DELAYING AGENTS (ARDAs)!
Vernakalant (RSD 1235) :!
§  Class III antiarrhythmic drug mainly acting on Ikur
(preferential effect on atrium), but owning also Na
blocking effect !
§  Other drugs : AVE0118, S9947/S20951, NP142, XenD0101/2 !
In those patients who converted
to sinus rhythm:!
–  Conversion was
successful with the first
dose in ~75%!
–  97.2% of patients remained
in sinus rhythm at 24
hours (pooled analysis of ACT I
and ACT III studies)!
% conversion to sinus rhythm
ACT Studies (Phase III)
!
Time (minutes)
The median time to conversion to sinus rhythm with vernakalant was
11 minutes (pooled analysis of ACT I and ACT III studies)!
Vernakalant was not successful in terminating primary atrial flutter!
Drugs and doses for pharmacological
conversion of (recent-onset) AF
www.escardio.org
ESC GUIDELINES 2010!
ithin
sion
ververt
n on
k of
6
In
lder
127
with
eart
emic
the
ared
no
vends a
% of
alant
ACT
conagodrug
with
who
verF of
verents
con-
Recommendations for pharmacological cardioversion
of recent-onset AF
Recommendations
Class a
Level b
Ref
C
When pharmacological
cardioversion is preferred
and there is no or minimal
structural heart disease,
intravenous flecainide,
propafenone, ibutilide, or
vernakalant are recommended.
I
A
120, 121,
123, 124,
126, 127,
131–134
In patients with AF ≤7 days
and moderate structural
heart disease [but without
hypotension <100 mm Hg,
NYHA class III or IV heart
failure, recent (<30 days) ACS,
or severe aortic stenosis],
intravenous vernakalant may
be considered. Vernakalant
should be used with caution in
patients with NYHA class I–II
heart failure.
IIb
B
120, 121,
124, 128
Intravenous vernakalant
may be considered for
cardioversion of postoperative
AF ≤3 days in patients after
cardiac surgery.
IIb
B
122
ACS ¼ acute coronary syndrome; AF ¼ atrial fibrillation; LoE ¼ level of evidence;
NYHA ¼ New York Heart Association.
a
Class of recommendation.
b
Level of evidence.
c
References.
www.escardio.org
ESC GUIDELINES 2012 UPDATE!
Recent-onset AF
Yes
Haemodynamic instability
Electrical
No
Patient/physician choice
Pharmacological
Emergency
Elective
Structural heart disease
Severe
Electrical
cardioversion
Intravenous
amiodarone
Ibutilide should not be given when significant left ventricular hypertrophy
(≥1.4 cm) is present.
b
Vernakalant should not be given in moderate or severe heart failure, aortic
stenosis, acute coronary syndrome or hypotension. Caution in mild
heart failure.
c
'Pill-in-the-pocket' technique – preliminary assessment in a medically safe
environment and then used by the patient in the ambulatory setting.
Moderate
None
Intravenous
ibutilidea
vernakalant b
Intravenous
flecainide
ibutilide
propafenone
vernakalant
Intravenous
amiodarone
Intravenous
amiodarone
Pill-in-the-pocket
(high dose oral)c
flecainide
propafenone
a
Figure 3 Indications for electrical and pharmacological cardioversion, and choice of antiarrhythmic drugs for pharmacological cardioversion
in patients with recent-onset AF.
7. Oral antiarrhythmic drug
therapy 2012 UPDATE!
GUIDELINES
patients with NYHA I or II heart failure because of increased risk of
hypotension. At present, vernakalant should be avoided in patients
with reduced LVEF (≤35%) because of limited experience.
www.escardio.org
The integration of vernakalant into the general schema for
pharmacological and electrical cardioversion is shown in Figure 3.
ESC
7.1 Upstream therapy
Type of Cardioversion
By country"
100%
6%
90%
80%
70%
66%
65%
56%
60%
50%
59%
77%
84%
91%
50%
94%
85%
96%
40%
30%
23%
Pharmacological CVr
Electrical CVr
w
ed
en
S
S
pa
in
5%
ol
an
d
an
y
G
er
m
Fr
an
ce
B
ra
zi
l
A
us
tr
al
ia
ta
l
0%
To
15%
10%
U
K
16%
P
10%
s
35%
50%
41%
N
et
he
rl
an
d
34%
44%
Ita
ly
20%
Drugs administered for
Pharmacological Cardioversion
By country"
100%
90%
80%
70%
13%
32%
25%
27%
16%
50%
39%
77%
100%
88%
40%
20%
4%
7%
41%
60%
30%
5%
12%
9%
70%
54%
53%
48%
53%
41%
10%
36%
19%
0%
Amiodarone
Flecainide
55%
Propafenone
CONCLUSIONS!
1- The choice of rhythm or rate control strategy is, in
most of the cases, an individual decision.
!
2- Sinus rhythm remains linked to a better prognosis,
but its maintenance must be obtained by drugs without
severe adverse effects or procedures without major
complications. !
3- Cardioversion keeps a major place in atrial fibrillation
management but there are important discrepancies in
the practices between countries.
!
5- Electrical is safer than pharmacological cardioversion
but Vernakalant seems to be a promising alternative in
recent atrial fibrillations. !
H
E
G
P