Riccardo Cappato, MDepsegypt.com/upload/122014/event/AF EP Workshop Dubai 4.14.pdf · UNIVERSITA...
Transcript of Riccardo Cappato, MDepsegypt.com/upload/122014/event/AF EP Workshop Dubai 4.14.pdf · UNIVERSITA...
UNIVERSITA DEGLI STUDI DI MILANO I.R.C.C.S POLICLINICO SAN DONATO
CENTRO PER LO STUDIO E LA TERAPIA DELLLE MALATTIE CARDIOVASCOLARI
“E. MALAN”
Electrophysiology Workshop 1-SVT
Atrial Fibrillation
Riccardo Cappato, MD
Mechanisms
Multiple wavelet hypothesis
Mechanisms of AF (Substrate)
Moe Arch Int Pharm
Ther 1962
Micro-reentry (Multiple)
Focal aconitine model
Focal activity (Aconitine model)
Mechanisms of AF (Trigger)
Focal trigger (in humans)
Transcatheter Ablation of AF
Focal origin of AF
Haissaguerre et al, 1994
Haissaguerre et al, 1994
Transcatheter Ablation of AF
Focal origin of AF
Experimental Mechanisms of Atrial Fibrillation
Automatic Focus Fixed Rotor Moving Rotor Mother Wave
Multiple Foci Unstable Circuits Multiple Wavelets
Focus +
Multiple Wavelets
Courtesy from Dr. Allessie
Focal pulmonary vein trigger (in humans)
Foci within PV
Mechanisms of AF (Trigger)
Haissaguerre et al, 1998
Transcatheter Ablation of AF
Focal origin of AF
Anatomiac substrate for PV triggers
Hocini et al, 2002
Anatomy of Pulmonary Veins
Electrophysiological substrate for PV triggers
(in dogs)
Hocini et al, 2002
Hocini et al, 2002
Fig. 2
Role of PVs in the Pathophysiology of AF
Oral et al, 2002
Role of PVs in the Pathophysiology of AF
PV mapping
Dominance ratio:
PV : LA = 7 : 3
Paroxysmal and Persistent AF
Permanent AF
A Large Data Base of Fibrillation Maps
from the Left and Right Atrium:
Acute AF Persistent AF
PV-area (seconds/patient): -
Total Seconds Analyzed:
LA (seconds/patient): -
312.8
Nr Patients: 24 25
12.0±4.1 RA (seconds/patient): 8.2±3.6
606.3
10.1±7.1
10.5±7.0
Total Nr of Maps: > 2.200 > 4.400
In More than 4.400 Maps of 24 Patients with Longstanding Persistent AF
NOT A SINGLE
Reentrant Circuit could be Detected
on the Epicardial Surface of
the Right or Left Atria
Big Surprise
Allessie et al, Circ Arrith Electr
Allessie et al, Circ Arrith Electr
Allessie et al, Circ Arrith Electr
0
Longitudinal Dissociation (mm/cm2)
0 10 20 30 40 50
0.5
1
1.5
2
Epicardial
Breakthrough
(# per cycle/cm2)
Diagnosis of the Substrate of AF?
'Focal' Fibrillation Waves
3cm de Groot et al. Circulation 2010
Two Recent Examples of Basket Maps
MV Anterior
MV Posterior
Sep
tal
Narayan et al. CircAE 2013
Diameter: 4.8 - 6.0cm
Perimeter: 15.0 - 18.8cm
Lat
eral
4.8 - 6 cm 4.8 - 6 cm
15 - 18.8 cm
Can We Trust the Maps?
Single Rotor ...Or Multiple
Breakthroughs?
Allessie et al. Circ Res 1978 Allessie et al. Circ Res 1978
Epi
Endo
de Groot et al. Circulation 2010
40 35 30 30 35 40ms
0 5 10 20 25 30ms 15
A Double Layer of Narrow Dissociated Wavelets that
Constantly 'Feed' Each Other.
Courtesy of Dr. Allessie
• Triggered activity, high-frequency local reentry and rapidly expiring
multiple multi-layer sleeves of electrically excited tissue have been
proven as possible mechanisms of unsustained or sustained fibrillatory
activity in animals and humans
• Stable rotor activity has been suggested as a possible mechanism of AF,
but the indirect nature of ist assessment requires more careful evaluation
before conclusive evidence is confirmed
Electrophysiology of Atrial Fibrillation
Conclusions
Mechanisms of AF (Excitation of gangionated plexi)
Ganglionated plexi
Mechanisms of AF (Excitation of gangionated plexi)
Ganglionated plexi
Mechanisms of AF (Excitation of gangionated plexi)
Ganglionated plexi
Focal trigger from other veins! (in humans)
Transcatheter Ablation of AF 2006
Focal origin of AF
Chen et al, 2002
Clinical models of isolation
Transcatheter Ablation of AF 2006
Haissaguerre et al, 2000
?
PV electrical disconnection
Isolation of Superior Vena Cava
Chen et al, 2002
Electrophysiological insights
(in humans)
Mechanisms of AF (Excitation of gangionated plexi)
Multiple PV isolation as therapeutic model
(for both initiation and perpetuation)
AF: Classification, Mechanisms & Hemodynamic Consequences
• Mechanisms other than PV trigger in play
• Loss of effectiveness over time
• Different mechanisms in paroxysmal vs. persistent AF
Why efficacy on short-term is lost at FU?
Surgical linear ablation
Cox et al, 1993
Transcatheter Ablation of AF 2006
at 1-yr FU, ca. 90%
of pts in SR!
Catheteter induced multiple PV isolation:
Drawbacks
Clinical Outcome at Different Steps (free of AADs)
Paroxysmal AF
(pts= 73)
Persistent AF
(pts= 47)
Asymptomatic after Step I 37 (50.1%) 11 (23.4%)
Asymptomatic after Step II 21 (28.8%) 27 (57.4%)
Asymptomatic after Step III 8 (10.9%) 5 (10.7%)
All asymptomatic at EoP 66 (89.8%) 43 (90.5%)
Outcome
Catheter Ablation of Paroxysmal vs Persistent AF
1.00
0.10
0.00
0 5 10 15 20
months FU
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
57 51 38 31 23 Pts at risk
Survival free of AF off AADs
Paroxysmal AF
Persistent AF
35 33 25 20 11
25
11
4
Catheter Ablation of Paroxysmal vs Persistent AF
Paroxysmal AF
(pts= 73)
Persistent AF
(pts= 47)
Age (yrs) 52.8±10.3 52.4±10.3 0.8
Male sex 61 (83.6%) 27 (76.6%) 0.7
Pts with AF duration longer than 5 yrs 4 (3.3%) 15 (31.9%) <0.01
Number of AA drugs 3.7±1.5 4.2±1.7 <0.05
Atrial flutter 22 (30.1%) 12 (25.5%) 0.6
Heart disease
- coronary artery 5 (6.8%) 2 (4.7%) 0.9
- valvular 9 (12.3%) 6 (12.7%) 0.9
Hypertension 15 (20.5%) 15 (34.0%) 0.6
Left atrium max TD (mm) 42.9±5.3 44.7±6.9 0.1
EF 0.51±0.09 0.53±0.08 0.8
FU duration (mos) 17.5±8.9 17.1±6.9 0.9
Pt characteristics P
longest A-PV 60 ms 80 ms 115 ms
pre-ABL1 pre-ABL2 pre-ABL3 post-ABL1 post-ABL2 post-ABL3
First procedure (day 1) Second procedure (day 93) Third procedure (day 234)
I
III
V1
ABL d
ABL p
Lasso 9 - 10
Lasso 8 - 9
Lasso 7 - 8
Lasso 6 - 7
Lasso 5 - 6
Lasso 4 - 5
Lasso 3 - 4
Lasso 2 - 3
Lasso 1 - 2
HIS
CS
shortest A-PV 50 ms 65 ms 105 ms 100 ms
A PV
A
A
A
A
A
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A
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A
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A
A
A
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
Modifiche della Ablazione sulla Durata della FA
Da prima a seconda
procedura
LSPV A-PV più breve (ms) 32 44.8 to 64.5 13 63.6 to 77.7
A-PV più lungo (ms) 67.3 to 98.0 98.0 to 100.0
RSPV A-PV più breve (ms) 29 26.5 to 45.5 14 44.8 to 57.1
A-PV più lungo (ms) 44.5 to 74.0 72.9 to 91.1
Pz Pz Da seconda a terza
procedura
LIPV A-PV più breve (ms) - - 20 41.8 to 52.8
A-PV più lungo (ms) - - 63.4 to 78.5
RIPV A-PV più breve (ms) - - 7 25.6 to 37.1
A-PV più lungo (ms) - - 45.6 to 64.3
AF: Classification, Mechanisms & Hemodynamic Consequences
• In pts with paroxysmal and persistent AF associated
with no heart disease or in the presence of mild heart
disease, multiple PV isolation is effective to reduce
precipitation and perpetuation of clinical arrhythmias
Pathophysiology
Mechanisms of AF in association
with complex substrate
Allessie et al, Circ Arrith Electr
Allessie et al, Circ Arrith Electr
AF: Classification, Mechanisms & Hemodynamic Consequences
• In pts with persistent or permanent AF and significant co-
morbidity,
– reentry does not appear to be the underlying mechanism
– focal activity may represent a surrogate of layer
breakthrough from electrical strings with short-life and
dynamic paths
Pathophysiology
substrate poorly amenable to catheter ablation!
What is Atrial Fibrillation?
• A symptom
• A disease
AF: Classification, Mechanisms & Hemodynamic Consequences
What is AF?
• It is intuitive to believe that it starts as an
epiphenomenon (caused by concomitant conditions,
sometimes difficult to be identieid)
• It has the potential to „take off and fly“ independently,
as a separate disease
– pathophysiologically
– clinically
AF: Classification, Mechanisms & Hemodynamic Consequences
What is AF?
Classification
• First detected AF
• Recurrent AF
– Paroxysmal
– Persistent
– Permanent (Long-standing persistent)
AF: Classification, Mechanisms & Hemodynamic Consequences
Classification
Fuster et al., 2001
ACC / AHA / ESC Guidelines
• Self-terminating within 1 week (usually 24-48 hours)
AF: Classification, Mechanisms & Hemodynamic Consequences
Paroxysmal AF
• Requires AADs or electrical cardioversion to restore
sinus rhythm
• Duration of less than one year
AF: Classification, Mechanisms & Hemodynamic Consequences
Persistent AF
• Does not resume sinus rhythm despite pharmacological
/electrical attempts or cardioversion not attempted based
on clinical judgement
• Longer than 1 year in duration
AF: Classification, Mechanisms & Hemodynamic Consequences
Permanent (long-standing persistent) AF
Assigned title in clinical perspective
Atrial Fibrillation: A Cardiologist’s Perspective
1. To interpret patient symptoms, fears and expectations
2. To put them into clinical perspective
3. To provide relief through appropriate treatment of
arrhythmia and precipitating cause(s)
4. To prevent from relapses of disease
Missions
Understanding of mechanisms and hemodynamic consequences
helps to prevent or mitigate symptoms and impact on prognosis!
Epidemiology
AF: Classification, Mechanisms & Hemodynamic Consequences
• Pts with younger age present more often with
paroxysmal AF
• Pts with longer hx of AF onset have a higher probability
to be in persistent / permanent AF
Epidemiology
Allessie et al, Circ 2001
AF: Classification, Mechanisms & Hemodynamic Consequences
I 4%
II-III 10%-26%
II-IV 12%-27%
III-IV 20%-29%
IV 50%
Prevalence of AF in pts with HF
Predominant
NYHA Class
Prevalence
of AF
Hemodynamic consequences of AF
AF: Classification, Mechanisms & Hemodynamic Consequences
• Low ventricular rate
• High heart rate
Hemodynamic consequences
Atrial Fibrillation: A Cardiologist’s Perspective
• Associated with atrial fibrillation
• Associated with precipitating events
• Subsequent to fibrillatory activity
Interpreting patient symptoms
AF: Classification, Mechanisms & Hemodynamic Consequences
• Major challenges are
– control of symptoms
– reduction of thromboembolic risk
Clinical approach
Atrial Fibrillation: A Cardiologist’s Perspective
• Palpitations
• Weakness
• Shortness of breath
• Dizziness
• Syncope
Interpreting patient symptoms
Associated with atrial fibrillation (classic)
Atrial Fibrillation: A Cardiologist’s Perspective
• Absence of symptoms
Interpreting patient symptoms
Associated with atrial fibrillation
not necessarily advantageous!
AF: Classification, Mechanisms & Hemodynamic Consequences
• Recent discoveries have led to improvement of our
understanding with regards to the mechanisms of AF in the
different clinical settings
• Improved knowledge has guided changing of diagnostic and
therapeutic approaches, also enabling non-surgical curative
therapy of this arrhythmia in selected pts
Conclusions
AF: Classification, Mechanisms & Hemodynamic Consequences
• Despite improvements in the understanding of AF
pathophysiology, treatment of symptoms associated with this
arrhythmia remains a delicate art incorporating overall clinical
judgement, identification and resolution, whenever possible,
of co-morbidity and precipitating conditions, re-assuring and
fine-tuning with patients expectations
Conclusions
Oral et al, 2002
Role of PVs in the Pathophysiology of AF
PV mapping
Dominance ratio:
PV : LA = 7 : 3
RAO view
Transcatheter Ablation of AF 2006
PV electrical disconnection
longest A-PV 60 ms 80 ms 115 ms
pre-ABL1 pre-ABL2 pre-ABL3 post-ABL1 post-ABL2 post-ABL3
First procedure (day 1) Second procedure (day 93) Third procedure (day 234)
I
III
V1
ABL d
ABL p
Lasso 9 - 10
Lasso 8 - 9
Lasso 7 - 8
Lasso 6 - 7
Lasso 5 - 6
Lasso 4 - 5
Lasso 3 - 4
Lasso 2 - 3
Lasso 1 - 2
HIS
CS
shortest A-PV 50 ms 65 ms 105 ms 100 ms
A PV
A
A
A
A
A
A
A
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PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
PV
Tops et al 2010
Tops et al 2010
Tops et al 2010
Tops et al 2010
Oral et al, 2002
Catheter Ablation of AF
Ouyang et al, 2004
PV and Posterior Wall Ablation
Examples of Lesion Sets LSPV
LIPV
RSPV
• ECG, including intracardiac EG, still most important imaging
tool after one hundred years
• Computer-assisted 3D mapping highly valuable for recognition
of target substrates
• New imaging technology may assist in energy delivery
Imaging and Atrial Fibrillation
Conclusions
Tops et al 2010
Atrial Fibrillation: A Cardiologist’s Perspective
• “Flying bird trying to get out of my thoracic cage”
• “Internal enemy attempting at my psycological integrity”
• “An alien heart beating with alien rhythm”
• “The falling in love feeling that takes you when you meet
your lover at first dates”
Interpreting patient symptoms
Associated with atrial fibrillation (unusual)
Atrial Fibrillation: A Cardiologist’s Perspective
• “…I cannot plan my holidays any longer, what to do if I
experience AF when far away from home?...”
• “…What if I get stroke?...”
• Gerrard, last year at Europe AF:
“…Because of my AF, my career is in danger. Will I be
able to secure my son’s future?....”
Interpreting patient fears
Atrial Fibrillation: A Cardiologist’s Perspective
• Relief from symptoms
– with drugs
– with pace-maker implant
– with ablation
• Freedom from oral anti-coagulants
• Freedom from risk of stroke
• Healing of underlying heart disease
Interpreting patient expectations
Atrial Fibrillation: A Cardiologist’s Perspective
• While sleeping
• After dinner
• Coffee
• Alcohol
• During effort
• Others
Interpreting patient symptoms
Associated with precipitating events
impairing quality of life and life style!
Atrial Fibrillation: A Cardiologist’s Perspective
• Weakness for hours or days
• Fear of new relapses
• Fear of stroke
• Impact on life style perspective
Interpreting patient symptoms
Subsequent to fibrillatory activity (in pts with AF)
Atrial Fibrillation: A Cardiologist’s Perspective
• Are symptoms associated with AF?
• If not, what is the cause of symptoms?
– co-morbidity? (heart disease - type and degree - ,
gastro-esophageal disease, others)
– psycological instability? (primary - mental
conflicts or imbalancement - ? secondary to AF?)
Symptoms in clinical perspective
correct diagnosis drives appropriate treatment and sets
reliable therapeutic expectations!
Atrial Fibrillation: A Cardiologist’s Perspective
• Drugs
– rhythm control
– rate control
– prevention of thromboembolic risk
• AV nodal modulation
• AV nodal ablation and pace-maker implantation
• Catheter ablation of arrhythmic substrate
Treatment of arrhythmias
Atrial Fibrillation: A Cardiologist’s Perspective
• Withdrawal of stimulating factors
– coffee, tee, alcohol
• Light and frequent meals
• Control of esophageal reflux
• Use of hypotensive agents, if hypertension (including
“borderline”?) is diagnosed
• Compensation for hormone imbalances (thyroid, supra-
renal, others)
Treatment of precipitating cause
Atrial Fibrillation: A Cardiologist’s Perspective
1. “…I am the doctor, I know what is best for you!...”
2. “…Here are the options, here are the pros and cons for each
of the choices available. What would you prefer?…”
Treatment of arrhythmias
Methodology
Atrial Fibrillation: A Cardiologist’s Perspective
• Drugs (palliative)
– rhythm control
– rate control
– prevention of thromboembolic risk
• AV nodal modulation (palliative)
• AV nodal ablation and pace-maker implantation (palliative)
• Catheter ablation of arrhythmic substrate (curative)
The paradigm of catheter ablation
Atrial Fibrillation: A Cardiologist’s Perspective
• Atrial fibrillation is frequent, mode of presentation
varies among pts and within pt, unpredictable,
invalidating, refractory to therapy, does not
disappear once for ever, carries a risk for stroke
Introduction
pts dream of a curative treatment, but know it will not be easy!
Atrial Fibrillation: A Cardiologist’s Perspective
Access of patients to therapy
Patients
Referring physicians Patients w/
previous experience
Internet
Catheter ablation
Atrial Fibrillation: A Cardiologist’s Perspective
Access of patients to therapy
Patients
*Referring physicians *Patients w/
previous experience
Internet
Catheter ablation
* “Peer-reviewed”-like modality of access!
Atrial Fibrillation: A Cardiologist’s Perspective
Access of patients to therapy
Patients
Referring physicians Patients w/
previous experience
*Internet
Catheter ablation
* “Abstract”-like (non-peer-reviewed) modality of access!
Transcateter Ablation of Atrial Fibrillation
Schwartz 1994 Left atrium (Maze-like) linear ablation
Haissaguerre 1996 Right (+ left) multiple linear ablation
Haissaguerre 1998 Focal triggering PV ablation
Pappone 2000 Left atrial circumferential PV ablation
Haissaguerre 2000 PV electrical disconnection
Ouyang 2004 Left atrial circumferential electrical disconnection
Nademanee 2004 Fragmented complex (left atrial) potential ablation
Jais 2004 PV electical disconnection + linear mitral isthmus block
Hocini 2005 PV electrical disconnection + LA roof linear block
Haissaguerre 2005 PV electrical disconnection + multiple linear ablation
Nakagawa 2007 Ganglionated plexi ablation
Author Year Technique
Transcateter Ablation of Atrial Fibrillation
• Referring physicians and communication with other patients
with previous experience on CA of AF provide a reasonable
level of filtering with regard to the quality of “sensible
information” released
• Self-promotion through Internet (or similar modes of
advertisement) is out of control in terms of quality and
reliability of “sensible data” released
Access of patients to therapy
Pros and cons
Transcateter Ablation of Atrial Fibrillation
• Relative proportion of different modalities used by patients for
access to catheter ablation of AF unknown and likely variable
from one center to another
• Prevalent distribution of modality of access according to self-
promoting models should raise concern in regulatory authorities,
at least with regard to verification of officially released data
Access of patients to catheter abaltion
Atrial Fibrillation: A Cardiologist’s Perspective
• First curative treatment of AF
• Variable success rates depending on type of AF, co-morbidity,
and investigator experience
• Setting pt expectations beyond the limit of objective evidence
causes additional discomfort
The paradigm of catheter ablation
Atrial Fibrillation: A Cardiologist’s Perspective
• Establishing a strong faithful relationship with these pts is the
very priority; this will help guiding pts through obtacles and
relapses
• Cure is a real possibility, but limits and concomitant therapies
should be discussed and integrated in the global scheme
The paradigm of catheter ablation
RAO view
Transcatheter Ablation of AF 2006
PV electrical disconnection
• Cicli di attività fibrillatoria più brevi nelle VP che nel tessuto
atriale adiacente
• L‘aumento progressivo nel no. di VP isolate associato a
– prolungamento consensuale del ciclo di FA
– interruzione della FA in corso (fino al 75% dei pz!)
Modifiche della Ablazione sulla Durata della FA
Evidenze elettrofisiologiche nell‘uomo
Studi in acuto
Evidenze cliniche
Oral et al, 2002
ULVP
LLPV
USPV
Ablation design
= electrical
disconnection
Catheter Ablation of AF
Fig. 1
• La maggior parte delle VP mostra recidive di conduzione 3-5
mesi dopo isolamento condotto con ablazione mediante RF
• In pz con FA PERS e nessuna o minima CP
– simile efficacia a quella ottenuta nella FA PAR con
isolamento puro di tutte le VP (about 90% success)
– dopo esclusivo isolamento delle VP, evidenza di
trasformazione da FA PERS a FA PAR
Modifiche della Ablazione sulla Durata della FA
Evidenze cliniche
Studi in cronico
• In pz con FA PAR, recidiva di FA e recidiva di conduzione VP
– l‘aumento dell‘intervallo A-PV correla in modo inverso
con la durata delle recidive di FA dopo ablazione della FA
Modifiche della Ablazione sulla Durata della FA
Evidenze cliniche
Studi in cronico
• Studi in acuto nell‘animale ed in acuto e cronico nell‘uomo
suggeriscono in modo indiretto il ruolo delle VP nella
perpetuazione della FA clinica
Modifiche della Ablazione sulla Durata della FA
Conclusioni
Mechanisms of AF (Excitation of gangionated plexi)
Efficacia cululativa in assenza di farmaci AA
FA parossistica
(pts= 72)
FA persistente
(pts= 47)
- Asintomatico dopo isol VP sup 31 (43.1%) 11 (23.4%)
- Asintomatico dopo isol tutte VP 57 (79.2%) 36 (76.6%)
- Asintomatico dopo consolidamento 65 (90.3%) 40 (85.1%)
Risultato
Modifiche della Ablazione sulla Durata della FA
IPOTESI:
•I trigger innescano multipli
circuiti da rientro
•Necessaria una certa quantità
di MASSA CRITICA per il
mantenimento dell’FA
MICROCIRCUITI DA RIENTRO
Moe Arch Int Pharm Ther 1962
… al concetto di massa critica
Sueda
Ann Thorac Surg 1997
circuiti di microrientro
Haissaguerre
NEJM 1998 foci delle
VP
L di M
Hwang
Circulation 2000
meccanismi necessari perFA