PFO- To Close for Comfort By: Vincent J.Caracciolo, MD FACC
PATENT FORAMEN OVALE PFO- congenital lesion that frequently persists into adulthood ( 25-30%)- autopsy and TEE studies. PFO prevalence higher in cryptogenic stroke, especially < 55 years old. Cryptogenic Stroke- occurs in absence of cardioembolic or large vessel source with a distribution not c/w small vessel distibution. Cryptogenic stroke- 40% of all ischemic strokes in patients < 55 years old
PFO embryology Septum primum grows to endocardial cushions When cushions and septum primum meetperforations form this is foramen primum Perforations then fuse forming Foramen secundum ( oxygenated blood to go from RA to LA) This is effectively the Foramen ovale At birth- Flap closure- due to O2 filling alveoli cause pulm arterioles to open and decrease PVR( this increase LA pressure and reduces RA pressure)
Prevalence PFO ( Patent Foramen Ovale) Congenital Cardiac lesion 25-30% healthy hearts at autopsy Most are asymptomatic Stroke patients 26% had PFO found during TEE, >45 years of age Increased size of PFO in older patients
Other defects associated with PFO Interatrial septal Aneursym- ( ASA)- ( 0.2 to 2%) redundant mobile Interatrial septal tissue. Moves 1-1.5 cm during cardiac-respiratory cycle- associated with PFOs Eustasian valve- juncture of IVC and RA Chiaria Network network of threads ad fibers in RA ( 2%)- strecth across RA from Eustacian valve attach to Interatrial septum
Inter-atrial septal aneursym
Atrial septal aneursym ( ASA) Increased prevalence in pts with thromboembolic CVA 8-15% 28% of CVA with normal carotid arteries Mecahnisms possible 1.) associated with PFO 2.)Fibrin- platelet particles adhere to LA side of aneursym and dislodge during ocillations
Eustacian Valve
Chiari Network
Cryptogenic Stroke ( CS) Absence of Cardiogenic emboli/large Vessel etiology/ distribution not c/w small vessel disease Increased risk of CS in patients with PFO Although PFO NOT associated with increased risk of RECURRENT stroke.
Cryptogenic Stroke
PFO and Stroke ( CS) Finding a PFO does NOT prove causal relationship Maybe innocent bystander ( 26% of all healthy hearts) Echo- start with transthoracic echo and then consider TEE/TCD with contrast TEE best- localize Flap Sedation may preclude adequate Valsalva- identify a PFO TCD only identify Right to left shunt shunt -not location of shunt
PFO and right to left shunting Can result in paradoxic embolus Transient increases in RA pressure- Valsalva Straining or Release phases- Defacate/Lifting/pushing heavy objects/ repetitive cough
Treatment of PFO Incidentally found PFO no follow up or treatment IF PFO is deemed causal to Cryptoigenic CVA- then medical therapy or closure of defect
Other clinical issues with PFO Migraine headache Decompression sickness Platypnea/orthodeoxia syndrome
WHAT is the DATA Isolated PFO- NOT associated with recurrent stroke Case Control Studies/meta analysis of them. 2000--- Increased risk of CVA if PFO, ASA or both in patients < 55 years old Odds ratio 3.1, 6.1, 15.6 Retrospective data risk of PFO and initial likelyhood of CVA History of Straining/hypercoaguable state/ multiple CVAs, Large PFO, Large right to left shunt, Spontaneous R to L shunt, PFO Flap mobility Another study showed no recurrent CVAs in a similar
Restrospective data Retrospective data PFO and initial risk of CVA History of Straining hypercoaguable state/ multiple CVAs Large PFO, Large right to left shunt, Spontaneous R to L shunt, PFO Flap mobility Prominent Eustasian valve or Chiari network Presence of Atrial Septal Aneursym
Prospective Studies Variable results French PFO- ASA study- 581 pts PICSS study- 630 pts CODICIA study- 486 patients NOMAS Study- 1100 pts SPARC study
French PFO- ASA Study- 581 pts ( case control) < 55 years old ( mean 42) with Cryptogenic stroke 37% had PFO 1.7% had ASA 8.8% had both PFO and ASA All pts got Aspirin 300 mg a day Isolated ASA group at 4 years no recurrence of CVA Isolated PFO group-( regardless of size) no CVA at 4 years Both PFO and ASA- increased risk of CVA ( 15% vs 4% in the absence of these abnormalities
PICSS sudy- 630 pts- Ischemic CVA 42% were Cryptogenic CVA (case control) TEE showed that the CS patients higher incidence of PFO- 39% vs. 29% average age- 59 years old Assigned to receive ASA 325 mg a day vs warfarin for INR 2-3.0 No association between PFO alone or PFO and ASA and recurrent risk of CVA or death ( different from French study) No reduction of recurrent CVA in pts on Warfarin vs. Aspirin
CODICIA study- 486 pts ( prospective) Transcranial Doppler quantify the magnitude of Right to left shunt- (RLSh) 2 year follow up, < 55 years old No association between magnitude of (RLSh) and recurrent CVA whether or not a Atrial Setpum aneursym was found or not
NOMAS STUDY 1100 patients (Prosepctive) Stroke free pts, > 40 years old Manhattan NY( mean age 69)- followed for about 6 years ( 80 months) TTE used to detect PFO PFO found in 14.9% patients ASA- 2.5% of pts. PFO alone or with ASA- statistically non-significant minor increased risk of CVA
SPARC study- 588 pts ( prosepctive) >45 years old, Olmstead Minnesoata- follow up- 5 years Used TEE- found 24% had PFO, 1.9% ASA PFO not significant risk for CVA after adjustment for comorbidities PFO size not associated with risk of CVA ASA 4 fold increase increase ( statistically not significant) only 11 pts had an ASA
Conclusions True risk of primary or recurrent ischemic Stroke associated with PFO or ASA difficult to estimate Case Control Trials- Association between Cryptogenic stroke and PFO- However 1/3 of all PFO found in Cryptogenic CVA are likely to be incidental findings Prospective trials PFO not associated with increased risk of recurrent CVA PFO + ASA- increased risk in French PFO/ASA study but not PICSS or CODICIA studies
2011 AHA/ASA guidelines PFO +/- ASA uncertain clinical importance in the development of first or recurrent CVA
Treatment for PFO/ASD and ASA for prevention of CVA 2011 AHA/ASA antiplatelet therapy is reasonable for cryptogenic CVA where no anticoagulation is necessary ( hypercoaguable patients) French PFO study- 216 pts with cryptogenic CVA + PFO Risk of recurrent CVA- 2.3% on Aspirin 300 mg qd Risk of recurrent CVA was 4.2% without PFO PFO + ASA- recurrent CVA- 15.2%- possible Warfarin or closure
PFO closure ( percutaneous vs surgical) No data on efficacy of closure on recurrent CVA Surgical closure- recurrent risk of CVA- 7-14% Sometimes residual shunt persists despite closure Lateral LA wall thrombus Increased atrial arrythmias with closure device
PC trial ( Amplatzer PFO occluder device) 414 pts (CS + PFO)-- < 60 year old PFO closure trials ( prospective/intention to treat) Closure 1 ( Starflex device) RESPECT 980 pts ( Amplatzer) ( CS + PFO_ = avg age- 46 years old 5 CVA vs 16 in the medical arm No statistically significant reduction in death/cva/tia When using intention to treat analyses but using raw data analysis it met statistical significance in CVA reduction alone ( p <.007%)
Starflex device
Amplatzer Septal Occluder device
TIA- 3.1 vs 4.1 % Closure 1 Trial Pts <60 with PFO + CS or TIA PFO closure (n= 447) vs med Rx (n= 462) Staflex PFO closure devise + ASA/Plavix x 6 months then ASA alone Med Rx- ASA or warfarin or both Endpoint CVA or TIA at 2 years No differences Combo of CVA/TIA ( 5.5 vs 6.8%) CVA- 2.9 vs 3.1%
Closure 1---subgroups Shunt size-- no differences in recurrent CVA ASA-- no differences Afib increased in PFO device arm 5.7% vs. 0% 5 of 12 strokes in Device arm- device thrombosis or afib related--??? Another devise could do better Critics feel study was underpowered and 2 year f/u not long enough ( i.e the CEA trials did not show benefit at 2 years) Suspicion that highest risk pts had closure outside the study
2012 ACCP guidelines Asymptomatic PFO or ASA NO antithrombotic therapy Incidental PFO and surgical closure may increase risk of post-op CVA PFO +/- ASA with cryptogenic CVA Aspirin If recurrent CVA on Aspirin or PFO + DVT then warfarin x 3 months then device closure vs. Aspirin
PFO with ASA (? Closure) French PFO/ASA study 51 pts ( < 55 years old) with Cryptogenic Stroke Recurrent CVA- 15.2% ( PFO+ ASA) on Aspirin Rx Suggest more aggresive therapy with Warfarin or closure BUT no difference in outcomes in the PICCS trial