Cardioembolic StrokeCardioembolic Stroke

Robert A. Felberg, MDRobert A. Felberg, MDStroke Program DirectorStroke Program DirectorDepartment of NeurologyDepartment of NeurologyGeisinger Medical CenterGeisinger Medical Center

Danville, PennsylvaniaDanville, Pennsylvania

Irregularly , Irregular Rhythm in Irregularly , Irregular Rhythm in a Regular elderly femalea Regular elderly female

87 year old Black Female87 year old Black FemaleHistory of Hypertension, well compensated History of Hypertension, well compensated Congestive Heart Failure, Hip Fracture 2 Congestive Heart Failure, Hip Fracture 2 years ago with pinningyears ago with pinningChief Complaint: LightheadednessChief Complaint: LightheadednessExam reveals: Exam reveals: – Irr. Irr. rhythmIrr. Irr. rhythm– EKG: Atrial Fibrillation rate 83/minEKG: Atrial Fibrillation rate 83/min

Normal Recent Thyroid StudiesNormal Recent Thyroid Studies

Irr. Irr. Rhythm in a Regular Irr. Irr. Rhythm in a Regular elderly femaleelderly female

How do you treat this patient?How do you treat this patient?

A: “Benign Neglect”A: “Benign Neglect”

B: Check Echo and Chemically Convert to B: Check Echo and Chemically Convert to NSR NSR

C: Aspirin 325mg Daily and write note C: Aspirin 325mg Daily and write note about fall risk in chartabout fall risk in chart

D: Warfarin 5mg Daily (Goal INR 2.0-2.5)D: Warfarin 5mg Daily (Goal INR 2.0-2.5)

Irr. Irr. Rhythm in a Regular Irr. Irr. Rhythm in a Regular elderly femaleelderly female

How do you treat this patient?How do you treat this patient?A: “Benign Neglect”A: “Benign Neglect”B: Check Echo and Chemically Convert to B: Check Echo and Chemically Convert to

NSRNSRC: Aspirin 325mg Daily and write note C: Aspirin 325mg Daily and write note

about fall risk in chartabout fall risk in chartD: D: Warfarin 5mg Daily (Goal INR 2.0-Warfarin 5mg Daily (Goal INR 2.0-

2.5)2.5)

Overview of TrialsOverview of Trials

Examples of Other Examples of Other StratificationsStratifications

A Warfarin Treatment GuidelineA Warfarin Treatment GuidelineBased Largely on SPAFBased Largely on SPAF

High risk embolism: one or more of the following- mitral stenosis, prosthetic valve, Previous TIA/Stroke, thyrotoxicosis, LV dysfctn, current systolic HTN, female >75, ECHO “smoke”, LA thrombusIntermediate embolism: none of the high risk, HX of HTNHigh bleeding: non compliance, active bleeding, recent ICHIntermediate bleeding: age >80, leukoareosis, HX of falls

Stroke in the YoungStroke in the Young

34 year old right handed white female. No 34 year old right handed white female. No significant PMHx. significant PMHx.

Sudden onset of Right Hemiparesis and Sudden onset of Right Hemiparesis and Aphasia.Aphasia.

Receives IV-TPA in the Emergency room Receives IV-TPA in the Emergency room with dramatic recovery.with dramatic recovery.

Stroke in the YoungStroke in the Young

MRI shows a small area of acute stroke in MRI shows a small area of acute stroke in the Left MCA territorythe Left MCA territory– And B/L embolic sub acute stroke in both And B/L embolic sub acute stroke in both

hemispheres as well as Right Cerebellumhemispheres as well as Right Cerebellum

Carotid U/S is NormalCarotid U/S is NormalNon-Smoker, Normotensive, Normal Non-Smoker, Normotensive, Normal LipidsLipidsNo history of DVT or miscarriageNo history of DVT or miscarriage

Stroke in the YoungStroke in the Young

How do you manage this patient?How do you manage this patient?

A.A. Antiplatelet therapy and dischargeAntiplatelet therapy and discharge

B.B. Check 2-d transthoracic echoCheck 2-d transthoracic echo

C.C. Check hypercoagulable LabsCheck hypercoagulable Labs

D.D. Check Tran-esophageal echo and Check Tran-esophageal echo and hypercoagulable labshypercoagulable labs

Stroke in the YoungStroke in the Young

How do you manage this patient?How do you manage this patient?

A.A. Antiplatelet therapy and dischargeAntiplatelet therapy and discharge

B.B. Check 2-d transthoracic echoCheck 2-d transthoracic echo

C.C. Check hypercoagulable LabsCheck hypercoagulable Labs

D.D. Check Tran-esophageal echo and Check Tran-esophageal echo and hypercoagulable labshypercoagulable labs

To Diagnose Cardioembolic To Diagnose Cardioembolic Stroke- You’ll need to look at Stroke- You’ll need to look at

the films!the films!The pattern of Stroke on The pattern of Stroke on imaging is key to finding imaging is key to finding the etiologythe etiology– Especially MRI imagingEspecially MRI imaging

Embolic StrokeEmbolic Stroke

Wedge ShapedWedge Shaped

PeripheralPeripheral

Typically CorticalTypically Cortical

Cardioembolic Strokes

•Multiple Multiple StrokesStrokes

•EmbolicEmbolic

•Separated by Separated by TimeTime

•Separated by Separated by LocationLocation

Cardioembolic Strokes

•Isolated PCA Isolated PCA or Superior or Superior Cerebellar Cerebellar StrokesStrokes

Cardioembolic Strokes

•Isolated Isolated Posterior Posterior Division MCADivision MCA

Clinical Clues to Suggest Clinical Clues to Suggest CardioembolismCardioembolism

Stroke during Valsalva ManeuverStroke during Valsalva Maneuver– CoughCough– SneezeSneeze– Sexual IntercourseSexual Intercourse

Pain: consider dissectionPain: consider dissection

Blue Toe SyndromeBlue Toe SyndromeSplinter HemorrhagesSplinter HemorrhagesRenal FailureRenal FailureCorneal hemorrhagesCorneal hemorrhages

Clinical Clues to Suggest Clinical Clues to Suggest CardioembolismCardioembolism

Clinical PointClinical Point– AFIB is the most common cause of stroke in AFIB is the most common cause of stroke in

patients over the age of 80patients over the age of 80

Clinical PointClinical Point– To evaluate for StrokeTo evaluate for Stroke– 2D echo is 2D echo is notnot valuable valuable

– TEE with Bubble study is the TEE with Bubble study is the national standard of carenational standard of care

Diagnosis of Cardioembolic Diagnosis of Cardioembolic SourcesSources

For Stroke EvaluationFor Stroke Evaluation– TEE is the Standard of CareTEE is the Standard of Care– TTE is not sufficient, not indicated, not sensitive, not TTE is not sufficient, not indicated, not sensitive, not

appropriate, and not likely to lead to diagnosis or appropriate, and not likely to lead to diagnosis or change in therapychange in therapy

Can not bill for TTECan not bill for TTE

An echo is not required for every patientAn echo is not required for every patient– Only those with a suspected cardiac sourceOnly those with a suspected cardiac source

Perform a Bubble study with the TEEPerform a Bubble study with the TEE

– TCD can be a non-invasive screen ScreenTCD can be a non-invasive screen Screen

TCD/PMD IMAGING FOR TCD/PMD IMAGING FOR DIAGNOSIS OF PFODIAGNOSIS OF PFO

courtesy Dr. Merrill Spencer

What are we looking for?What are we looking for?

The micro bubbles The micro bubbles will cross the right will cross the right to left shuntto left shunt

Enter the cerebral Enter the cerebral circulation circulation

Be detected by Be detected by TCDTCD

Courtesy of Mark Moehring Spencer Technolgy

Patent Foramen Ovale:•Significant cause of stroke in the Significant cause of stroke in the youngyoung

•PFO found in 40% of Idiopathic PFO found in 40% of Idiopathic Stroke cases Stroke cases

PFO in stroke: Pathophysiology

Paradoxical Embolism

Focal Thrombosis

• Lechat, NEJM 1988• Webster, NEJM 1988• De Belder 1992• Di Tullio 1992• Hausmann 1992• Cabanes 1993

54%

50%

13%

47%

50%

56%

10%

15%

3%

4%

11%

18%

< 0.01

< 0.01

< 0.01

< 0.01

< 0.01

< 0.01

Cryptogenic Stroke

Control P value

Incidence of PFO in cryptogenic stroke versus normals

RARA

LALARVRV

The MAS StudyThe MAS StudyA Multi-Center Prospective Observational Study to A Multi-Center Prospective Observational Study to determine the rate of recurrent stroke/TIA in young determine the rate of recurrent stroke/TIA in young idiopathic stroke patients with sub-group comparison of idiopathic stroke patients with sub-group comparison of those with septal abnormalities to those with normal those with septal abnormalities to those with normal septal findings.septal findings.

Mas Mas JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste JL, Arquizan C, Lamy C, Zuber M, Cabanes L, Derumeaux G, Coste J; Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. J; Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent cerebrovascular events associated with patent foramen Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or bothovale, atrial septal aneurysm, or both.. N Engl J Med. 2001 Dec N Engl J Med. 2001 Dec 13;345(24):1740-6. 13;345(24):1740-6.

BackgroundBackground

Despite many theories regarding therapy, there Despite many theories regarding therapy, there is poor natural history data regarding the is poor natural history data regarding the absolute and relative risk of PFO and ASA in the absolute and relative risk of PFO and ASA in the setting of “stroke in the young”setting of “stroke in the young”

An observational study was undertaken to An observational study was undertaken to determine the natural history of PFO/ASA vs determine the natural history of PFO/ASA vs non-PFO/ASA in young idiopathic strokenon-PFO/ASA in young idiopathic stroke– NOTE: Not a comparison of stroke patients vs. normal NOTE: Not a comparison of stroke patients vs. normal

controls.controls.

Clarification: “ASA”:Clarification: “ASA”:

AspirinAspirin

Atrial Septal AneurysmAtrial Septal Aneurysm

Trial DesignTrial DesignConcurrent Idiopathic Stroke Patients Concurrent Idiopathic Stroke Patients – age 18-55age 18-55

All patients had a standard stroke evaluationAll patients had a standard stroke evaluation– Excluded those for whom cause was foundExcluded those for whom cause was found

Lacunar strokeLacunar strokeAtrial fibrillationAtrial fibrillationHypercoagulable StatesHypercoagulable States

All patients had a TEE with bubble studyAll patients had a TEE with bubble studyPatients were split into 4 groups and followed for 2 yearsPatients were split into 4 groups and followed for 2 years

No septal abnormalityNo septal abnormalityPFO onlyPFO onlyASA onlyASA onlyPFO+ASA in combinationPFO+ASA in combination

Kaplan–Meier Analysis of Survival without Vascular Events (Brain Infarction, Myocardial Infarction, Peripheral Embolism, or Death from Vascular Causes), According to Plaque Thickness in the Aortic Arch Proximal to the Ostium of the Left Subclavian Artery.

•The French Study of Aortic Plaques in Stroke Group. NEJM 334:1216-1221

•331 patients with stroke331 patients with stroke

•>60 years of age>60 years of age

•TEE Confirmed Aortic TEE Confirmed Aortic AtheromaAtheroma

•GradedGraded

•Aortic plaques >4 mm thick Aortic plaques >4 mm thick (including the thickness(including the thickness of the of the aortic wall) aortic wall)

•Recurrent brain infarctionRecurrent brain infarction

•relative risk, 3.8;relative risk, 3.8;

•P = 0.0012 P = 0.0012

•All vascularAll vascular events events

•relative risk, 3.5; relative risk, 3.5;

•P<0.001P<0.001

Mas, J.-L. et al. N Engl J Med 2001;345:1740-1746Mas, J.-L. et al. N Engl J Med 2001;345:1740-1746

Kaplan-Meier Estimates of the Risk of Recurrent Cerebrovascular Events within

Four Years after the Index Stroke

What What IS IS PICCS?PICCS?

PPatent Foramen Ovale atent Foramen Ovale IIn n CCryptogenic ryptogenic SStroke troke SStudytudy

Substudy of WARRSSubstudy of WARRS

– A study designed to compare ASA and A study designed to compare ASA and warfarin for the prevention of recurrent warfarin for the prevention of recurrent ischemic stroke in patients with prior (<30 ischemic stroke in patients with prior (<30 days) noncardioembolic ischemic strokedays) noncardioembolic ischemic stroke

What What IS IS PICCS?PICCS?

Patients eligible if event not attributed to Patients eligible if event not attributed to high-grade carotid stenosis for which high-grade carotid stenosis for which surgery was planned and not associated surgery was planned and not associated with an inferred cardioembolic sourcewith an inferred cardioembolic source

Composite endpoint of death or recurrent Composite endpoint of death or recurrent ischemic stroke over two years after ischemic stroke over two years after enrollmentenrollment

PICSS PICSS ResultsResults

Death was the endpoint in 23% of patientsDeath was the endpoint in 23% of patientsComposite endpoint for entire group (at 2 yrs) Composite endpoint for entire group (at 2 yrs) 13.2% in aspirin group vs 16.5% in warfarin 13.2% in aspirin group vs 16.5% in warfarin group (p=NS)group (p=NS)Composite endpoint in group with cryptogenic Composite endpoint in group with cryptogenic stroke and PFO (n=98): 17.9% in ASA group vs stroke and PFO (n=98): 17.9% in ASA group vs 9.5% in warfarin group (p=NS)9.5% in warfarin group (p=NS)

This group of 98 (4.4% of the original 2206) This group of 98 (4.4% of the original 2206) patients represents the only group of patients represents the only group of cryptogenic stroke/PFO patients enrolled in cryptogenic stroke/PFO patients enrolled in a randomized trial (not placebo-controlled) a randomized trial (not placebo-controlled) of medical therapy.of medical therapy.

NMT Medical, Inc.

The STARFlex Occluder:

Double umbrella design with auto centering microsprings

Framework is MP35n

Tissue matrix is polyester fabric (Dacron)

The Amplatzer OccluderThe Amplatzer Occluder

PFO in Embolic Stroke

Annual recurrence rate (Stroke, TIA,) after PFO closure

• Hung et. al. Circulation 2000 3.2 %• Meier; Circulation Feb 2000 2.5 %• Sievert et al, Abstract AHA Nov 2001, 3.1 %• Palacios, Circulation, Aug 2002 0.9%

• Lock; Circulation Jan 2003 3.0%

March 2003

Very little information to

make an informed treatment decision

Especially if you Especially if you wish to rely on wish to rely on

evidence and not evidence and not anecdoteanecdote

Remember: Some evidence is more

reliable than others

PFO in Embolic Stroke

What do we really know about recurrent event rates for each form of therapy?

Only that a definitive, Only that a definitive, randomized, controlled randomized, controlled

study is needed!study is needed!

March 2003

Investigating the PFO Stroke connection

NMT Medical, Inc.

RESPECT TRIALAGA Medical

Other Cardioembolic Sources of Other Cardioembolic Sources of StrokeStroke

Artificial ValvesArtificial Valves– New devicesNew devices– New AnticoagulantsNew Anticoagulants

ArrythmiasArrythmias– Atrial FibrillationAtrial Fibrillation– Frequent PAC’sFrequent PAC’s

CardiomyopathyCardiomyopathy– WARCEF trialWARCEF trial

Aortic Arch Aortic Arch AtheromaAtheroma

•Atherosclerotic disease of the aortic Atherosclerotic disease of the aortic arch is foundarch is found in 60 percent of patients in 60 percent of patients 60 years of age or older who have60 years of age or older who have

had brain infarctionhad brain infarction

•Usually divided into threeUsually divided into three groups groups according to the thickness of the wall according to the thickness of the wall of the aorticof the aortic archarch

• <1 mm<1 mm

• 1 to 3.9 mm1 to 3.9 mm

•>4 mm>4 mm

<1 mm<1 mm

>4 mm