Download - Cardioembolic Stroke
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