Tecniche mininvasive di chiusura
difetti interatriali : ombrellini & Co
B.Castiglioni
Cardiologia Interventistica
UO cardiologia II
Ospedale di Circolo – Varese -
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Forame Ovale Pervio (FOP-PFO)
•
•
Valvola unidirezionale che permette il passaggio di
sangue dall’atrio destro all’atrio sinistro.
Causato dalla non fusione, nel postparto, del
septum secundum al septum primum.
Prevalenza
•
•
•
Popolazione generale all’autopsia
Adulti sani all’ECO TT
Adulti sani all’ECO TE
Cardiologia II -Varese -
27%
10-18%
26%
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Rischio di ricorrenza annuale di Stroke
in presenza di PFO (in trattamento medico)
N. Pazienti
Stroke
TIA
Lausanne Study (Neurology 1996)
140 pt
1,9%
1,9%
Mas (N Engl J Med 2001)
267pt
(solo PFO)
(PFO+ASA)
0,6%
3,8%
0,7%
1,3%
Homma (Circulation 2002)
203 pt
6.5%
10,2%
Berne Group (J Neurosurg Psych 2002)
159 pt
(pz. con 1 ev)
(pz. con + ev)
1,8%
3,6%
3,7%
6,3%
Homma (PICSS, JACC 2003)
Cardiologia II -Varese -
44 pt
(PFO+ ASA)
8%
BC 2012
Chiusura percutanea PFO
Rischio di Ricorrenza annuale di Stroke
dopo Occlusione Percutanea
Studi precedenti
Wahl (J Interv Cardiol 2001)
Carminati (Ital Heart J 2001)
Beiztke (J interv Cardiol 2001)
Bruch (Circulation 2002)
Braun (JACC 2002)
Martin (Circulation 2002)
Onorato (J Interv Cardiol 2003)
Cardiologia II -Varese -
n. pazienti
stroke
92
0%
2.0%
0%
0%
0%
0%
0%
0.5%
0%
2.0%
0%
1,6%
0%
1.7%
0.9%
n.r.
132
35
162
66
276
110
256
TIA
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Windecker S, J Am Coll Cardiol , 2004
Schuchlenz HW, In J Cardiol 2005
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
J Am Coll Cardiol, 2009,53;2014-2018
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Forame ovale pervio ad alto rischio
Fattori anatomici
Dimensioni canale (ampiezza >4 mm)
Presenza aneurisma setto interatriale
Grado di shunt (passaggio microbolle >25 durante Valsalva al TEE)
Shunt di elevato grado in basale
Presenza di valvola di Eustachio ( residua valvola che dirige sangue da VCI a FO)
Presenza di rete di Chiari ( connessioni fibrose tra v. Eustachio ed altre strutture AD)
Fattori clinici-emodinamici
Ictus durante /dopo Valsalva
TVP (embolia paradossa)
Trombofilia ( mutazione fattore V Leiden …)
Ictus al risveglio in malattia apnee notturne
Aumento pressione cavita’ destre ( embolia polmonare, IT, infarto Dx)
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
• L’aneurisma del setto interatriale
(ASA) è una deformità localizzata
“sacciforme”, generalmente a
livello della fossa ovale, che sporge
nell’atrio destro o sinistro o in
entrambi.
Porzione ridondante ed altamente mobile
del setto interatriale.
•
La prevalenza di ASA riportata negli studi
TTE varia tra 0.08% e 1.2%.
•
Gli studi con TEE riferiscono una
prevalenza tra il 2% e il 10%.
•
Nella popolazione pediatrica la
prevalenza riportata con TTE è 0,9% 1,7% nei bambini, 4.9% nei neonati.
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Associazione PFO ASA
Pazienti con associazione
PFO e ASA colpiti da ictus
cerebrale costituiscono un
sottogruppo ad elevato
rischio di recidive in cui
debbono essere
considerate strategie
preventive alternative
all’aspirina.
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Valvola di Eustachio
Cardiologia II -Varese -
BC 2012
A Prospective, Multicenter, Randomized Controlled Trial to
Evaluate the Safety and Efficacy of the STARFlex Septal Closure
System Versus Best Medical Therapy in Patients with a Stroke or
Transient Ischemic Attack due to Presumed Paradoxical
Embolism through a Patent Foramen Ovale
Anthony J Furlan MD
Gilbert Humphrey Professor
Chairman Department of Neurology
Co-Director Neurological Institute
University Hospitals Case Medical Center
Case Western Reserve University School of Medicine
For the CLOSURE I Investigators
Trial Sponsor: NMT Medical Boston
Study Design
•
Prospective, multi-center, randomized, open-label, two-arm superiority trial
designed to test whether PFO closure using STARFlex® plus medical therapy is
superior to medical therapy alone for preventing recurrent stroke or TIA in patients
with cryptogenic stroke or TIA and a PFO
– IRB approved at each site and all patients signed informed consent
•
Study population: Patients 60 years old or younger with a cryptogenic stroke or TIA
and a PFO documented by TEE, with or without atrial septal aneurysm, within 6
months of randomization
–
DVT, hypercoagulopathy excluded
•
Primary endpoint : 2-year incidence of stroke or TIA, all cause mortality for the first
30 days, and neurological mortality 31 days to 2 years
•
Followup at 1 month, 6 months, 12 months and 24 months by a board certified
neurologist
– repeat TEE at 6 months all patients and 12/24 months if residual leak
2 Year Primary Endpoint ITT
Composite
Stroke
TIA
STARFlex
Medical
n = 447
n = 462
Adjusted
P value*
5.9%
7.7%
0.30
(n=25)
(n=30)
3.1%
3.4%
(n=12)
(n=13)
3.3%
4.6%
(n=13)
(n=17)
0.77
0.39
*Adjusting performed using Cox Proportional Hazard Regression and adjusting for related patient characteristics including:
age, atrial septal aneurysm, prior TIA/CVA, smoking, hypertension, hypercholesterolemia
Composite Primary Endpoint
Baseline Shunt and Atrial Septal Aneurysm (TEE)
STARFlex
N=400
Medical
N=451
P value
Trace
shunt
7.0%
8.0%
0.75
(n=8/114)
(n=10/126)
Moderate
shunt
5.3%
8.4%
(n=7/132)
(n=12/143)
3.6%
5.3%
(n=3/84)
(n=3/57)
6.4%
8.5%
(n=15/236)
(n=20/236)
4.9%
6.5%
(n=7/142)
(n=9/139)
Substantial
shunt
No atrial septal
aneurysm
Atrial septal
aneurysm
0.31
0.62
0.38
0.58
Adverse Events
STARFlex
N=402
Medical
N=458
P value
Major vascular
complications*
3.2%
0.0%
<0.001
Atrial fibrillation
5.7%
0.7%
<0.001
(n= 14/23 periprocedural)
(n=3)
2.6%
1.1%
(n=10)
(n=4)
Deaths (all non
endpoint)
0.5%
0.7%
(n=2)
(n=3)
Nervous system
disorders
3.2%
5.3%
(n=12)
(n=20)
Any SAE
16.9%
16.6%
(n=68)
(n=76)
Major bleeding
(n =13)
0.11
ns
0.15
ns
*Perforation LA (1); hematoma >5cm at access site (4); vascular surgical repair (1); peripheral nerve injury (1);
procedural related transfusion (3);retroperitoneal bleed (3)
CONCLUSIONS
• CLOSURE I is the first completed, prospective, randomized,
independently adjudicated PFO device closure study
• Superiority of PFO closure with STARFlex® plus medical
therapy over medical therapy alone was not demonstrated
–
–
–
–
no significant benefit related to degree of initial shunt
no significant benefit with atrial septal aneurysm
insignificant trend (1.8%) favoring device driven by TIA
2 year stroke rate essentially identical in both arms (3%)
• Major vascular (procedural) complications in 3% of device arm
• Significantly higher rate of atrial fibrillation in device arm (5.7%)
– 60% periprocedural
CONCLUSIONS
• Alternative explanation unrelated to paradoxical embolism
present in 80% of patients with recurrent stroke or TIA
–
–
–
–
•
cryptogenic stroke and TIA include multiple etiologies
in many patients with cryptogenic stroke or TIA a PFO may be coincidental
diagnostic criteria for paradoxical embolism are imprecise
potential efficacy of PFO device closure in better defined patient subgroups
requires further study
Percutaneous closure with STARFlex® plus medical therapy does not
offer any significant benefit over medical therapy alone for the prevention
of recurrent stroke or TIA in patients < age 60 presenting with
cryptogenic stroke or TIA and a PFO
STARFlex Technical Success
Procedural success
Thrombus by TEE
STARFlex
n=402
95% CI
90.0%
(86.7%,92.8%)
1.0%
(n=4; stroke in 2 at days 4, 52)
Effective closure
No recurrent stroke or TIA in
patients with residual leaks
TEE 6 mos
86.1% closed
(82.1%,89.4%)
TEE 12 mos
86.4% closed
(82.5%,89.8%)
86.7% closed
(82.8%,90.0%)
TEE 24 mos
Procedural success was defined as successful delivery of one or more STARFlex devices to the site during the index procedure, deployment of the
device at the intended site, and removal of the delivery system without a major procedural complication prior to discharge. Effective closure was defined
as procedural success with either grade 0 (none) or 1 (trace) residual shunt by TEE.
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Metodica
•
•
•
•
•
•
•
•
Profilassi antibiotica – Eparinizzazione
Assistenza anestesiologica – sedazione profonda
Puntura percutanea vena fem. Dx
Posizionamento TEE (o Eco I.C.)
Posizionamento guida angiografica in AS e quindi in VP
Avanzamento in AS di catetere tipo Mullins Rilascio del
doppio disco Amplatzer (prima in AS poi in AD)
Controllo del corretto posizionamento e rilascio del device
Ricerca di eventuale shunt residuo
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Rischi procedurali (6%)
Sanguinamenti maggiori
1%
Embolizzazione device
1.7%
Terapia e Follow-up
Duplice terapia antiaggregante
per 3-6 mesi
ASA ……
Controlli clinici-Eco TT - Eco TE
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Cardiologia II -Varese -
BC 2012
Chiusura percutanea PFO
Chiusura del PFO
Problematiche presenti
NON Evidence based
NON priva di rischi
Costi
Cardiologia II -Varese -
Protocollo multidisciplinare
Centri riferimento
Collaborazione multidisciplinare
Nuove Codifiche,
delibere regionali
Possibili soluzioni
Cardiologo
Neurologo
Carico lavoro
Esperienza
Amministratori
Regione
BC 2012
Chiusura percutanea PFO
“In patients aged <55 years,
PFO and ASA are associated
with ischemic stroke, and
some causality can be
inferred if no other causes
are identified”
Cardiologia II -Varese -
“closure is reasonable in
patients who have had an
ischemic event that is
cryptogenic (particularly in
young patients)”
BC 2012