Patent Foramen Ovale and Atrial Septal Aneurysm: Current Perspectives

Jesse Jorgensen, MD Carolina Cardiology Consultants

November 19, 2011

Objectives

1. Identification of Patent Foramen Ovale (PFO)/Atrial Septal Aneurysm (ASA) and its role in acute ischmeic stroke

2. Treatment of PFO/ASA for stroke prevention

Basic Atrial Septal Anatomy

PFO Devices

• Amplatzer (FDA approval Dec 2001) • HELEX (FDA approval Aug 2006)

Amplatzer Septal Occluder

Kurt Amplatz, MD, May 2006, Twin Cities Business Magazine

Amplatzer Septal Occluder

• 72 braided nitinol wires • Self-Expandable • Polyester material for occlusion • Nickel allergy contraindication

(8% women, 2% men)

Amplatzer Septal Occluder

GORE HELEX Septal Occluder

• ePTFE patch material (Gore-Tex) supported by a single nitinol wire frame

• ASD size up to 18 mm

PFO: Guilty or Innocent Bystander?

• Incidence ~25% in the general population • Associated with paradoxical embolism (esp stroke),

migraine headache, decompression sickness, platypnea orthodeoxia, left-sided valvular involvement with carcinoid

• Associations largely based on retrospective case-control studies

• The management of PFO following stroke among the most controverstial areas in cardiology

PFO Case: A.F.

53 yo woman with symptoms since 1991 of fatigue, diagnosed with fibromyalgia and chronic fatigue syndrome. Now legs are weak, vertigo, progressive left arm weakness and paresthesias. Chronic, severe right frontal migraines. MRI: right sided lesions, multiple sclerosis vs emboli. Lumbar puncture nondiagnostic.

TEE: PFO with Atrial Septal Aneurysm

TEE: positive bubble study

PFO prevalence in young stroke patients

Neurology 2000;55:1172-1179

PFO prevalence in stroke patients

A. Age <55

A. Age >55

Neurology 2000;55:1172-1179

PFO and Cryptogenic Stroke

• While more than 50% of stroke pts younger than 45 have a PFO, observational studies have not found an increased risk of CVA from an incidentally detected PFO over time

• Surgical closure of incidental PFOs has no long term benefit and increases risk of perioperative stroke

J Am Coll Cardiol 2006;47:440-445 JAMA 2009;302(3):290-297

PFO and Cryptogenic Stroke

• Frequency of DVT ranges from 10-57% (5 of 53 patients in one series, 24 of 42 patients in another)

• Hypercoagulable state rare in this population • High Risk Anatomic Features: Atrial Septal Aneurysm Wide (≥4mm) separation between septum primum &

secundum Greater degree of right-to-left shunting Shunting at rest

Am J Cardiol 1997;80:1066-1069 N Engl J Med 2005;353:2361-72 Ann Intern Med 1993;119:461-465

Thrombus-in-Transit: the smoking gun?

J Am Soc Echocardiogr 2007;20:1219.e6-e8

PFO and Migraine

• Migraine is present in 10-12% of the population • Association between PFO with right to left shunt

and migraine (esp with aura) • Migraine resolution following PFO closure for

other indication

PFO prevalence in migraine pts

CCI 2007 69:9-14

Effect of PFO closure on migraine

CCI 2007 69:9-14

PFO: Options for Therapy

• ASA • Plavix • ASA + Plavix • Coumadin • PFO closure: surgical vs. percutaneous

PFO Medical Therapy

• Warfarin-Aspirin Recurrent Stroke Study (WARSS): 2,206 pts with prior CVA randomized to ASA 325 QD or Warfarin (target INR 1.4-2.8). 2y recurrent CVA or death similar

• Patent Foramen Ovale in Cryptogenic Stroke Study (PICCS, substudy of WARRS), 250 pts had TEE revealing 98 PFOs (39%). PFO did not increase risk of subsequent CVA or death

• In PFO pts, 2y risk of CVA or death was 17.9% vs 9.5% with ASA vs. Coumadin (p=NS), minor hemorrhage 8.7% vs. 22.9% (P=NS)

PFO Medical Therapy

• Meta-analysis (including PICCS): annual CVA or death 4.7% on Coumadin vs 8.9% on ASA (RR .53, .18-1.58)

• Warfarin is not clearly superior but is often recommended in practice as first-line therapy

• ASA ± thienopyridine reasonable alternative • American Academy of Neurology 2004: “clinicians who

encounter patients with cryptogenic stroke and PFO (and/or ASA) should encourage them to consider participating in research protocols”

Long Term Efficacy of Anticoagulation vs Antiplatelet Therapy

Recurrent ischemic events long term in patients arbitrarily assigned to coumadin or aspirin SUBOPTIMAL

Circ 2009;120:1837-1841

PFO: Transcatheter Therapy

• First reported in 1992 • Variety (>12) of device designs • In general, safe, effective, high procedural

success, low risk of periprocedural complications, favorable results long term

• >200,000 percutaneous PFO closures worldwide

(No controlled trials have compared PFO closure with medical therapy)

Data Summary: PFO closure vs. medical therapy

Ann Intern Med. 2003;139:753-760

Incidence of recurrent stroke by age

PFO: Transcatheter Therapy

• THERE IS NO FDA-APPROVED PFO DEVICE • FDA HDE for 2 devices (Amplatzer PFO

Occluder and CardioSeal) withdrawn August 2006; target population was recurrent embolic CVA with anticoagulation failure (exceeded limit of 4,000 pts annually)

PFO Closure Device Trials

Circ 2009;120:1837-1841

Off Label Use of Devices for PFO

• Amplatzer Cribriform Septal Occluder (labeled for treating multiple ASDs): really the PFO Occluder by a different name

• HELEX occluder (labeled for ASD) • CardioSeal (labeled for VSD)

PFO: Guidelines Summary

,AHA/ASA (IIb)

**AHA/ASA: “Insufficient data exist to make a recommendation about PFO closure in patients with a first stroke and a PFO”

Summary of Nonrandomized Trials on the Effects of PFO Closure on Migraine

Clev Clin J Med 2007;74 suppl 1:S114-S117

MIST I results

Dowson A. i2 Summit at the American College of Cardiology 2006 Scientific Sessions; March 13, 2006; Atlanta, GA.

End point PFO closure

Sham p

Headache cessation (n) 3 3 NS

50% reduction in headache days (%)

42 23 0.038

Reduced headache burden (%) 37 17 0.033

•Prospective RCT of PFO closure in treating severe therapy-resistant migraine with aura •147 English patients, 1:1 PFO closure:sham •6 month follow up •Controversial trial

Circ 2008;177:1397-1404

Randomized PFO Migraine Trials

Circ 2009;120:1837-1841

PFO Case: A.F.

53 yo woman with symptoms since 1991 of fatigue, diagnosed with fibromyalgia and chronic fatigue syndrome. Now legs are weak, vertigo, progressive left arm weakness and paresthesias. Chronic, severe right frontal migraines. MRI: right sided lesions, multiple sclerosis vs emboli. Lumbar puncture nondiagnostic.

TEE: PFO, right to left shunt, atrial septal aneurysm

PFO in the real world: Tedy Bruschi

• Feb 2005: left sided weakness, visual field cut, & headache 4 days after playing in Super Bowl

• Diagnosed with Stroke by CT, found to have PFO

• PFO closed March 2005 • Returned to work Oct 2005,

played through 2008 season

• Dec 18, 2005: small ischemic stroke at age 77

• PFO discovered, placed on Lovenox, scheduled for PFO closure Jan 5

• Jan 4, 2006: massive cerebral hemorrhage, ? related to cerebral amyloid angiopathy

PFO in the real world: Ariel Sharon

PFO Closure with ICE

PFO Closure with ICE

PFO closure: follow up

• ASA long term • Plavix + Abx proph x 6 months is the convention • TTE at 3, 6, and 12 months

PFO Case Follow Up

6 months post procedure, doing well with stable neurologic symptoms, no procedural complications, migraines resolved (bonus!)

PFO Summary

• Randomized trials need to be completed—both for stroke and migraine indications

• Currently, PFO closure offered as alternative to medical therapy following first cryptogenic stroke (ignores the guidelines)

• PFO closure for migraine not recommended outside of clinical trial

THANK YOU!