Professional Documents
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Case Example
41 yo AAF admitted to Neurology with acute stroke Right sided hemiparesis and aphasia, found to have left MCA territory stroke Mild HTN, otherwise no risk factors, not taking contraceptives No prior stroke, no history of A.fib Brain MRI shows large superficial stroke MRA and carotid duplex shows no significant intra-cerebral or extra-cranial vascular disease Serologies and hypercoagulability studies unremarkable TTE negative for LV thrombus, normal EF
Case Example
She makes a good recovery over the first few days of hospital stay and continues to work with PT/OT & Speech She has been started on Aspirin, Atorvastatin TEE with bubble study performed, reveals PFO with R to L shunt on Valsalva, in addition to atrial septal aneurysm LE venous US negative for DVT Cardiology Consulted: Please evaluate for possible PFO closure to reduce risk of recurrent stroke
Call Dr Lotun?
Outline
Introduction Diagnosis Clinical Scenarios of Importance Cryptogenic Stroke Migraines with Aura Indications for Closure & Controversies Devices & Techniques
Introduction
Definition
o A Patent Foramen Ovale (PFO) is a communication between the atria that begins at the fossa ovalis in the RA and transverses to the ostium secundum on the left atrial side o Exists during fetal life to allow flow of oxygenated blood from the IVC to pass from RA to LA, bypassing the lungs o Typically closes shortly after birth as the newborn takes its first breath and LA pressure rises and exceeds RA pressure o Distinction between PFO and ASD is that PFO represents failure of fusion of septum primum and septum secundum, whereas ASD represents a failure in the formation of the interatrial septum
Prevalence
o Autopsy studies : Around 27% of population have PFO o More common in younger patients, prevalence declines with age
Diagnosis
Seen on echocardiography (TTE or TEE) as a communication between the atria allowing right to left shunting as detected by color/spectral Doppler, or by an agitated saline contrast injection (i.e. a bubble study) Shunt may not be apparent without Valsalva or cough, so these maneuvers should be performed to rule out a PFO TEE w bubble study considered the reference standard with sensitivity about 90% compared with autopsy findings
Diagnosis
Scuba Diving
Presence of a PFO considered a risk factor for decompression illness in scuba divers
o Series of 30 patients w decompression illness evaluated with 2D Echo o Prevalence of PFO was 37% (vs 5% in their group of healthy controls) o Prevalence was higher (61%) in those with severe signs and symptoms
Incidence of decompression illness is however very low, and there are currently no recommendations for divers to be routinely screened For those with diagnosed PFO, it is not a contraindication to diving and no indication for closure simple routine precautions advised
Platypnea-Orthodeoxia Syndrome
Platypnea = Dyspnea induced by assuming upright posture and relieved with recumbency Orthodeoxia = Arterial desaturation in the same setting Causes divided into 3 main categories
o Intra-cardiac Shunting, Intrapulmonary Shunting & V/Q mismatch
PFO with R to L shunting is associated with this condition as an example of intra-cardiac shunt Important to distinguish from intra-pulmonary shunting that may be associated with this syndrome (e.g. cirrhosis causing hepatopulmonary syndrome)
o Bubbles crossing R to L within 4 cardiac cycles of injection favors primary intra-cardiac lesion, whereas later than 4 cycles favors intra-pulmonary site.
Higher prevalence of PFO in patients with stroke, particularly patients with Cryptogenic Stroke
o Raises two important questions: 1. Can PFO be causally implicated in a patient with CS who has a PFO? 2. If the above is true, will PFO closure reduce rate of recurrent stroke?
Thrombus in Transit
Timing is everything
Thrombus in Transit
Thrombus in Transit
Patient with PE
Thrombus PFO
Other possibilities:
2. Thrombus formation on LA side, with abnormalities of the interatrial septum acting as nidus 3. Passage of unmeasured vasoactive substances escaping pulmonary degradation
Lechat et al. NEJM 1988; 318: 1148-52 Webster et al. Lancet 1988; 11-2
o All looked at risk of recurrent stroke in patients with PFO and history of cryptogenic stroke o Found no increased risk of recurrent stroke with PFO compared to without o Exception: Mas et al noted patients with both PFO and ASA had 15.2% risk of stroke at 4 years, which was significantly higher than those without ASA HR 4.17 (1.47-11.84)
Association Causation
PICSS Study
PICSS Study
Indication: Secondary prevention for patients with CS or TIA Study design: Retrospective analysis of patients who had PFO closure for above reason Technique: TEE/ICE was used intra-procedure Devices: Amplatzer Septal Occluder in 99% (AGA) or CardioSEAL in 1% (NMT Medical) Baseline Characteristics:
o Results: N = 352 patients, 100% procedural success 12 procedural complications (3.4%) o Atrial flutter, A. fib, vasovagal reaction o Retroperitoneal bleed, tamponade, transient diplopia Mean f/u of 37 months o Recurrence rate for combined endpoint of ischemic stroke/TIA 1 year 0.9%; 4 years 2.8% 16 deaths during follow-up, none adjudicated as related to device or to ischemic neurologic event o However: Cohort study only, no control arm
Closure 1
Preliminary Results released 6/17/10 by NMT Medical:
o PFO closure with STARFlex device did not meet primary endpoint of superiority in recurrent stroke or TIA risk reduction compared to medical therapy o Press release quotes a small but not statistically significant reduction in outcomes with PFO closure (though details in terms of numbers not reported) o PFO with the STARFlex device showed a good safety profile, with complications similar to that of standard medical therapy, and a very low rate of thrombus formation o Full details and analysis of data is pending
PC-Trial
Centers in Europe and Australia Active but no longer recruiting Enrolling patients with CS and PFO Device = Amplatzer PFO Occluder Goal enrollment was 500 patients Projected completion was in 2007 but has been extended
CLOSE Trial
Single Center in France Enrolling patients with CS and PFO ages 16 to 60 Any PFO device can be used Goal of 900 patients Estimated completion 2012
Summary of Guidelines
HDE withdrawn in 2006, as patient population found to be in excess of 4000 pts per year in the US Access to these devices now through Investigational Device Exemption All use outside this IDE considered off-label
Devices
STARFlex (NMT Medical)
Devices
CardioSEAL (NMT Medical)
Devices
Amplatzer PFO Occluder (AGA Medical Corporation)
Mounted on double-umbrella framework Umbrellas connected by microsprings and serve as selfcentering mechanism
BioSTAR Study
62 patients Prospective cohort study 93.5% referred with h/o either CS or TIA All implanted with either TEE or ICE guidance
BioSTAR Study
BioSTAR Study
Bottom-line:
o o o o Appears safe compared with other devices Low rate of recurrent embolic events Unique properties suggest it may be more favorable than prior devices Still lacks the support of data from: Large number of patients Randomized study with true control arm Longer term follow-up
Summary
PFO has association with Cryptogenic Stroke and Migraine with Aura, but difficult to prove causal relationship in individual patients Percutaneous closure of PFO may reduce risk of recurrent embolic events in patients with CS, but as yet unproven in randomized trial (several trials in progress) PFO closure appears beneficial for MA in observational studies but only RCT failed to show a benefit (trials in progress) Percutaneous PFO closure appears generally safe and newer devices may offer some advantages Essential to enroll patients in clinical trials to further evaluate safety and efficacy