Transcript PFO Closure: a critical overview of recent data

PFO Closure :
a critical overview of recent data
Ramesh Daggubati, MD FACC FSCAI
Director of Interventional Cardiology
East Carolina University
Greenville, NC USA
Disclosure Statement of Financial Interest
Consultant to St. Jude Medical
Background: Cryptogenic Stroke and PFO
Cryptogenic stroke remains a major challenge
 PFO-related strokes, i.e. due to paradoxical embolism, have been
strongly implicated as a possible cause
 Patients age 20-54 are now a larger percentage of all stroke
patients and among first ever strokes in the younger population
there is growth in ischemic strokes1
 Cost of stroke is significant, with over $94B2,3 spent each year in
the US and EU alone – cost implications with young patients are
immense, based on the loss of productivity and long-term care
1.
2.
3.
Kissela, BM, Khoury, JC, Alwell, K,et al. Age at stroke Temporal trends in stroke incidence in a large, biracial population. Neurology 2012;79:1781-1787
Roger, V, Go, A, Lloyd-Jones, D, et. Al. Heart Disease and Stroke Statistics – 2012 Update: A Report from the American Heart Association. Circulation. 2012; 125:e2-e220
Allender,S, Scarborough, P, Peto, V, et al European cardiovascular disease statistics 2008
Transcatheter Closure vs Medical Therapy
SECONDARY STROKE PREVENTION
(recurrent event rate %)
Khairy 2003
Meta-analysis
Windecker 2004
Retrospective
Schuchlenz 2005
Retrospective
PFO Closure
Medical Therapy
0-4.9%
3.8-12%
-
8.5%/4 ys
24.3%/4 ys
p = 0.05
0.6%/year
13%/year Aspirin
5.6%/year Warfarin
p < 0.001
Khairy et al. Ann Intern Med 2003; 139: 753-760;
Windecker et al. J Am Coll Cardiol 2004; 44: 750-758
Schuchlenz et al. J Cardiol 205; 101:77-82
PFO Closure :
a critical overview of recent data
(1)
Lessons from Randomized Control Trials
General Limitations of Randomized Control
Trials (RCTs) addressing PFO Therapies
 Low event rates: < 2% recurrent stroke/year
 Difficult extrapolation of RCTs results to unselected
populations in clinical practice
 Short follow-up duration (2-5 years) to compare longterm efficacy and safety of life-long drug treatments
with interventional procedures
General Limitations of Randomized Control
Trials (RCTs) addressing PFO Therapies
 Difficult to generalize any result obtained with
specific implantable device to other devices
 Long enrollment phase
homogeneity of therapies
raising
concerns
on
 Very difficult to perform RTCs when PFO closure
can be obtained off-label.
 Selection bias with low-risk pts enrollment
General Limitations of Randomized Control
Trials (RCTs) addressing PFO Therapies
 Higher risk pts get their PFO closed “off label” thus
making harder to show a difference between device and
medical treatment
 Closure I had and equal recurrence rate in the device
arm because the CardioSeal/Starflex was
thrombogenic and had a 14% large residual shunt. This
does not mean that other trials, with better devices,
have to be negative as well
RANDOMIZED PFO CLOSURE TRIALS
Device
PC-Trial
Principal
Investigator
500
400
5y
completed
APO
Saver JL
900
980
2y
completed
STARflex
Furlan A,
Reisman M
1600*
900
2y
completed
Helex
Kasner SE
664
5y
Enrolling
Cardia
Mooney MR
300
1y
Recruiting
Mas JL
900
3-5 y
Recruiting
(2003) US & Canada
REDUCE
(2008) US & Denmark
CARDIA PFO
Stroke Trial
State
Meier B
(2003) US
CLOSURE I
F-up
APO
(2000) Europe & Australia
RESPECT
n° pts
Planned Enrolled
100
(2007)
CLOSE
(2007) France
* 2007 (april) FDA consent to reduce numbers to 900; APO= Amplatzer PFO Occluder
RANDOMIZED PFO CLOSURE TRIALS
• CLOSURE I enrolled
– Wrong patients
– Wrong PFOs
– Wrong device
Subpopulation Differential Treatment Effect
24
What does RESPECT learn us?
• That device closure is feasible
• That device closure is safe (complications 0-1.6%)
• That device closure is effective
PFO Closure :
a critical overview of recent data
(2)
How to select patients
How to select PFO patients ?
•
•
The management of patients with
Cryptogenic
Stroke
and
PFO
is
controversial
High level unbiased data do not yet exist
to guide our clinical decisions with these
challenging patients
How to select PFO patients ?
PFO related conditions
•
•
•
•
•
•
•
•
Transient Ischemic Attack (TIA) / Crytogenic Stroke
Migraine with Aura
Orthostatic desaturation in the setting of platypnea-orthodeoxia
syndrome
Decompression illness and ischemic cerebral lesions in divers
Paradoxical air embolism and desaturation during neurosurgical
procedures (posterior fossa surgey)
Obstructive sleep apnoea
Peripheral and coronary embolism
Refractory hypoxaemia in patients with right ventricular infarction or
pulmonary hypertension
SELECT APPROPRIATE PATIENTS - I
• Cardioembolic stroke
– DWI multiple early lesions
– Lesions in different territories
– Posterior or cortical distribution
• rule out dissection
There were no differences in occurrence of multiple lesion
pattern in patients with cryptogenic stroke compared to
patients with PFO neither for the entire group nor for a
subgroup of young stroke patients less than 50 years.
Patients with PFO showed a significantly higher incidence of
multiple lesions in the posterior circulation
SELECT APPROPRIATE PATIENTS - II
•
Collect evidence favouring paradoxical embolism as the most likely mechanism
 Exclude paroxysmal AF with appropriately long Holter monitoring (or,
better, telemetry)
– Systematic investigation of factors predisposing to DVT:
Prolonged immobilization – recent prolonged travel
Leg trauma
Surgery – Anesthesia
Coagulation disorders [Factor V Leiden - Prothrombin (G20210A)]
– Search for anatomical variants and DVT in unusual locations
– D-Dimer measurement
– Stroke on awakening (association with OSAS)
– Valsalva at onset
– Exclusion of ANY other RF
SELECT APPROPRIATE PATIENTS - II
•
Collect evidence favouring paradoxical embolism as the most likely mechanism
 Exclude paroxysmal AF with appropriately long Holter monitoring (or,
better, telemetry)
– Systematic investigation of factors predisposing to DVT:
Prolonged immobilization – recent prolonged travel
Leg trauma
Surgery – Anesthesia
Coagulation disorders [Factor V Leiden - Prothrombin (G20210A)]
– Search for anatomical variants and DVT in unusual locations
– D-Dimer measurement
– Stroke on awakening (association with OSAS)
– Valsalva at onset
– Exclusion of ANY other RF
SELECT APPROPRIATE PATIENTS - III
• Identify “pathological” PFOs:
– Association with ASA
– Large (> 2mm) PFO size
– Eustachian valve
– >1 cm long tunnel
– Large shunt on bubble test
– Permanent shunt
SELECT APPROPRIATE PATIENTS - IV
• Look for systemic embolization
– Occult PE
SELECT APPROPRIATE PATIENTS - IV
• Look for systemic embolization
– Occult PE
– Silent heart lesions
– Renal infarcts (?)
Conclusions: Subclinical myocardial infarctions
determined in CMRI were observed in 10.8% of
patients with PFO after a first cryptogenic cerebral
ischemic event. Our results strengthen the
pathophysiologic role of a PFO with paradoxical
embolism in patients with cryptogenic cerebral
ischemic events .
Wohrle et al.J Am Coll Cardiol Img, 2010; 3:833-839
SELECT THE APPROPRIATE DEVICE
• Low profile devices so as to
minimize:
–
–
–
–
Anatomical distortion
Risk of local thrombosis
Risk of late erosion
Risk of inducing AF
SELECT THE APPROPRIATE LENGTH OF F-UP
Management of patients with cryptogenic stroke and
patent foramen ovale
 Recently, a consensus statement of recommendations
was developped by approaching Italian Scientific
Societies to address the urgent need of adopting a
comprehensive and rationale workflow in the management
of patients with Cryptogenic Stroke and PFO
The goal was to organize a common approach that may be
shared by different specialists
Catheter Cardiovasc Interv. 2012 Aug 31. doi: 10.1002/ccd.24637
[Epub ahead of print]
MANAGEMENT OF PATIENTS WITH CRYPTOGENIC
STROKE AND PATENT FORAMEN OVALE
Cryptogenic Stroke/TIA (symptomatic/asymptomatic)
& PFO with R-L Shunt
First cryptogenic event
without anatomical/clinical
risk factors
Medical therapy
Anatomical risk factors
Atrial septal aneurysm
Large PFO (>4 mm)
Basal R-L shunt
Eustachian valve >10 mm
Chiari network
Long PFO tunnel
Any cryptogenic event
(first or recurrent) on
AP and/or OA therapy
Cath PFO closure
as an alternative
to medical therapy
Cath PFO closure
Clinical risk factors
Multiple ischemic lesions on CT/MR
Recurrent clinical events
History of DVT/PE and/or Thrombophilia
Valsalva-associated embolic event
Ischemic event on arousal (OSAS)
Long travel/immobilization associated event
Simultaneous systemic/pulmorany embolism
MANAGEMENT OF PATIENTS WITH CRYPTOGENIC
STROKE AND PATENT FORAMEN OVALE
•
•
A multidisciplinary shared approach may become a
basis for a joint management of these patients, while
waiting for more consistent evidences
Team-based, multidisciplinary clinical judgment on an
individual basis still remains the core of decisionmaking
PFO Closure :
a critical overview of recent data
(3)
The future of PFO Closure
The future of PFO Closure
In my view, the challenge now for
the endovascular community is to
refine the selection criteria
The future of PFO Closure
“Some more indications”
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Decompression sickness
Platypnea-orthodeoxia Syndrome
Major orthopaedic surgery
Posterior fossa surgery
Obstructive sleep apnoea
Peripheral or coronary embolism
The future of PFO Closure
Results with newer devices
may be better !
Take Home Message
There is a trend towards:
– Devices with less material
– Bioresorbable devices
– Non-device closure techniques
The future of PFO Closure
 lower profile and less foreign material could reduce
risk of thrombus formation
 softer devices and in-tunnel devices could reduce
septal distortion and risk of atrial fibrillation
 bioresorbable devices and non device closure
techniques could prevent unknown long-term device
related complications