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Structural Heart Defects and Stroke

Structural Heart Defects and Stroke

George V. Moukarbel, MDAssistant Professor of MedicineInterventional CardiologyDirector, Heart Failure & LVAD ProgramAssociate Director, Cardiovascular Fellowship ProgramThe University of Toledo Medical Center

George V. Moukarbel, MDAssistant Professor of MedicineInterventional CardiologyDirector, Heart Failure & LVAD ProgramAssociate Director, Cardiovascular Fellowship ProgramThe University of Toledo Medical Center

Stroke Update Symposium Nov. 14, 2014

Objectives:Objectives:• Review structural heart defects that are

associated with stroke and the therapy to prevent stroke events

• Discuss the cardiac evaluation of patients presenting with stroke

• Outline the treatment of stroke patients who have underlying structural cardiac lesions

• Review structural heart defects that are associated with stroke and the therapy to prevent stroke events

• Discuss the cardiac evaluation of patients presenting with stroke

• Outline the treatment of stroke patients who have underlying structural cardiac lesions

DisclosuresDisclosures

• I have no disclosures relevant to this presentation

• I have no disclosures relevant to this presentation

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Structural Heart

Disease Spectrum

Structural Heart

Disease Spectrum

Patent foramen

ovale

Atrial septal defect

Ventricular septal defect

Hypertrophic cardiomyopathy

Left atrial appendage

Left ventricular aneurysm

Patent ductus

arteriosus

sinus of valsalva

aneurysm

Vascular fistulae

Valvular heart disease

Paravalvular leak

Heart Disease and Strokes:Leading Killers in the United States Heart Disease and Strokes:Leading Killers in the United States

Cause 1 of every 3 deathsMore than 1 of 3 (83 million) U.S. adults currently

lives with one or more types of cardiovascular disease. Over 2 million heart attacks and strokes each year• $444 B in health care costs and lost productivity• Greatest contributor to racial disparities in life

expectancy

Cause 1 of every 3 deathsMore than 1 of 3 (83 million) U.S. adults currently

lives with one or more types of cardiovascular disease. Over 2 million heart attacks and strokes each year• $444 B in health care costs and lost productivity• Greatest contributor to racial disparities in life

expectancy

Roger VL, et al. Circulation 2012;125:e2-e220Heidenriech PA, et al. Circulation 2011;123:933–47

Stroke SubtypesStroke Subtypes

Ischemic 80%

Hemorrhagic 20%

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Stroke

IschemicHemorrhagic

Lg. vesselSmall vessel Embolic

Eur Neurol 2007;57:212–218

Causes of Ischemic Stroke in Young AdultsCauses of Ischemic Stroke in Young Adults

50%50%15%15%

10%10%

5%5%

10%10% 10%10%

CARDIOEMBOLIC SOURCESCARDIOEMBOLIC SOURCES

NonvalvularAtrial Fibrillation

NonvalvularAtrial Fibrillation

Acute MIAcute MI

LV thrombusLV thrombusValvular heart

diseaseValvular heart

disease

Prostheticvalves

Prostheticvalves

Other lesscommon sources

(PFO, ASA,aortic debris, etc.)

Other lesscommon sources

(PFO, ASA,aortic debris, etc.)

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Definition of CardioembolicStrokeDefinition of CardioembolicStroke

• Embolism of material forming on or crossing through the atrial or ventricular wall or heart valves

• Particles/debris embolize to the arterial circulation of a brain region• Embolus is: Thrombus, fat, air,

cancer cells, clumps of bacteria, etc…

• Embolism of material forming on or crossing through the atrial or ventricular wall or heart valves

• Particles/debris embolize to the arterial circulation of a brain region• Embolus is: Thrombus, fat, air,

cancer cells, clumps of bacteria, etc…

Clinical Characteristics of Cardioembolic StrokeClinical Characteristics of Cardioembolic Stroke

• Sudden in onset, with maximum neurologic deficit at once

• Decreased consciousness at onset

• Embolism to other brain regions• Embolism to other organs• Palpitations at onset

• Sudden in onset, with maximum neurologic deficit at once

• Decreased consciousness at onset

• Embolism to other brain regions• Embolism to other organs• Palpitations at onset

• Generally worse prognosis than thrombotic strokes as the area infarcted is usually larger due to large emboli

• Emboli from the heart most often lodge in the MCA, PCA, and infrequently ACA

• Generally worse prognosis than thrombotic strokes as the area infarcted is usually larger due to large emboli

• Emboli from the heart most often lodge in the MCA, PCA, and infrequently ACA

Clinical Characteristics of Cardioembolic StrokeClinical Characteristics of Cardioembolic Stroke

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Cardiac Workup of the Patient with Stroke: What to Look ForCardiac Workup of the Patient with Stroke: What to Look For

• Cardiac arrhythmias• Cardiac murmurs• Signs of Heart Failure• Recent MI• Concomitant diseases ( eg.

endocarditis)• Signs of systemic embolism

• Cardiac arrhythmias• Cardiac murmurs• Signs of Heart Failure• Recent MI• Concomitant diseases ( eg.

endocarditis)• Signs of systemic embolism

• Neurologic Exam• Cardiac Exam• Vascular Exam (Carotid Bruits,

Peripheral Pulses)• Dermatologic

• Splinter hemorrhages and needle tracks (endocarditis)

• Xanthoma (hyperlipidemia)• Ophthalmologic

• Neurologic Exam• Cardiac Exam• Vascular Exam (Carotid Bruits,

Peripheral Pulses)• Dermatologic

• Splinter hemorrhages and needle tracks (endocarditis)

• Xanthoma (hyperlipidemia)• Ophthalmologic

Physical ExamPhysical Exam

Cardiovascular Diagnostic Testing for Patients With StrokeCardiovascular Diagnostic Testing for Patients With Stroke

• Carotid ultrasonography• Transthoracic echocardiography• Transesophageal echocardiography• Electrocardiogram• Prolonged ECG monitoring with Holter

or event loop recorder (external or implantable)

• Blood studies (Thrombophilia panel)

• Carotid ultrasonography• Transthoracic echocardiography• Transesophageal echocardiography• Electrocardiogram• Prolonged ECG monitoring with Holter

or event loop recorder (external or implantable)

• Blood studies (Thrombophilia panel)

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High Risk Medium Risk Low/Unclear Risk

LV hypokinesia / aneurysm

Bioprostetic valve

LV systolic dysfunction

? Myxomatous MVP

Patent foramen ovale

Atrial septal aneurysm

Spontaneous echo contrast

SSS

Embolic Risk of Various Cardiac Lesions

Atrial fibrillation/flutter

Recent anterior MI

Mechanical valve

Rheumatic mitralstenosis

Thrombus / tumor (myxoma)

Endocarditis

Additional (Minor risk) sourcesAdditional (Minor risk) sources• Calcific Aortic Valve or Bicuspid

Aortic Valve• Mitral Annular Calcification• Fibroelastomas (benign tumors on

valves)• Lambl’s excrescences (filliform

outgrowths from free borders of valves)

• LV regional wall motion abnormality• Aortic arch atheromatous plaques

• Calcific Aortic Valve or Bicuspid Aortic Valve

• Mitral Annular Calcification• Fibroelastomas (benign tumors on

valves)• Lambl’s excrescences (filliform

outgrowths from free borders of valves)

• LV regional wall motion abnormality• Aortic arch atheromatous plaques

TreatmentTreatment• Primary prophylaxis depends on

the particular risk factor but centers primarily around anti-coagulation, especially in the high-risk group (except for endocarditis and myxoma)

• Primary prophylaxis for medium or low risk factors is less clear as benefit of anti-coagulation is not yet proven

• Primary prophylaxis depends on the particular risk factor but centers primarily around anti-coagulation, especially in the high-risk group (except for endocarditis and myxoma)

• Primary prophylaxis for medium or low risk factors is less clear as benefit of anti-coagulation is not yet proven

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Stroke Is the Most Common and Devastating Complication of AFStroke Is the Most Common and Devastating Complication of AF

• All-cause stroke rate with AF is 5% per year

• AF - independent risk factor for stroke• ~5-fold increase in stroke risk• ~15% of all strokes caused by

AF• Stroke risk increases with

age

• Stroke risk persists asymptomatic AF

• All-cause stroke rate with AF is 5% per year

• AF - independent risk factor for stroke• ~5-fold increase in stroke risk• ~15% of all strokes caused by

AF• Stroke risk increases with

age

• Stroke risk persists asymptomatic AF

Fuster V, et al. Circulation. 2006;114:e257-e354.Wolf PA, et al. Stroke. 1991;22:983-988. Page RL, et al. Circulation. 2003;107:1141-1145. Hart RG, et al. J Am Coll Cardiol. 2000;35:183-187.

90% of Clots Reside in the Appendage90% of Clots Reside in the Appendage

Stroke Risk in AF: CHADS2 ScoreStroke Risk in AF: CHADS2 Score

Risk Factor Points

C Congestive HF 1

H Hypertension 1

A Age ≥ 75 1

D Diabetes 1

S2 Prior Stroke/TIA 2

Gage BF, et al. JAMA. 2001;285:2864-2870.

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Risk of Stroke Without Warfarin inNational Registry of Atrial Fibrillation (NRAF) by CHADS2 Score

Risk of Stroke Without Warfarin inNational Registry of Atrial Fibrillation (NRAF) by CHADS2 Score

0 1 2 3 4 5 60

5

10

40

50

CHADS2 Score

Gage BF, et al. JAMA. 2001;285:2864-2870.

*Crude stroke rate per 100 patient-years

Medical Management: Anticoagulant

Surgical Excision (Appendectomy)

Transcatheter Device Closure

Clot Prevention: Management Options

Warfarin vs Placebo inStroke Prevention in AF

100% 50% 0% -50% -100%

AFASAK-1

SPAF

BAATAF

CAFA

SPINAF

EAFT

ALL Trials

Favors Warfarin Favors Placebo/Control

Hart R, et al. Ann Intern Med. 2007;146:857-867.

Warfarin reduces incidence of stroke by ~64%

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Aspirin vs Placebo inStroke Prevention in AF

Favors Placebo/Control

Antiplatelet therapy reduces incidence of stroke by ~22%

All Trials

100% 50% 0% -50% -100%

AFASAK-1 SPAF IEAFTESPS-II

LASAF, daily

UK-TIA, 300 mg daily

Favors Antiplatelet

LASAF, alternate day

UK-TIA, 1200 mg daily

JAST

Aspirin Trials SAFTESPS II, Dipyridamole

ESPS II, Combination

Hart R, et al. Ann Intern Med. 2007;146:857-867.

Warfarin vs Antiplatelet Therapy inStroke Prevention in AF

100% 50% 0% -50% -100%

Favors Warfarin Favors Antiplatelet

AFASAK I AFASAK II

Chinese ATAFSEAFTPATAF

SPAF II, ≤ 75 yrs

SPAF II, >75 yrs

Aspirin trials

SIFAACTIVE-W

NASPEAF

All Trials

Warfarin reduces incidence of stroke by ~39%

Hart R, et al. Ann Intern Med. 2007;146:857-867.

Antithrombotic Therapy – A CHADS2Risk Score-based Approach

Antithrombotic Therapy – A CHADS2Risk Score-based Approach

0

• None*• Aspirin

1

• OA*• DAPT

≥2

• OA*• DAPT

OA: oral anticoagulationDAPT: dual antiplatelet therapy (ASA/Clopidogrel)* Preferred strategy

ACCP 2012 Guidelines

Additional risk factors:Female genderAge 65 to 74 yVascular disease

CHA2DS2-VASc

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Newer TherapiesFactor Xa Inhibitors and Direct Thrombin Inhibitors

Newer TherapiesFactor Xa Inhibitors and Direct Thrombin Inhibitors

Harenberg J. Semin Thromb Hemost. 2009;35:574-586.

Tissue Factor/VIIa

IX

IXa

X

Xa

VIIIa

Va

II IIa

Fibrinogen Fibrin

RivaroxabanApixabanEdoxaban(DU-176b)

Dabigatran

Dogliotti et al. Clin. Cardiol. 2013

Novel Oral Anticoagulants in AtrialFibrillation: A Meta-analysis of Large,Randomized, Controlled Trials vs Warfarin

Novel Oral Anticoagulants in AtrialFibrillation: A Meta-analysis of Large,Randomized, Controlled Trials vs Warfarin

Trials included in analysis: SPORTIF III, SPORTIF IV, RE-LY, ROCKET AF, ARISTOTLE

Non-Pharmacologic ApproachesNon-Pharmacologic Approaches

• Surgery• Percutaneous left atrial exclusion• Surgery• Percutaneous left atrial exclusion

Lariat

AmplatzerWatchman

Class IIb, level of evidence B2014 AHA/ASA Stroke Guidelines

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When to start anticoagulation in patients with

stroke in the setting of AF?

When to start anticoagulation in patients with

stroke in the setting of AF?

Within 14 days for most patients.

Delay beyond 14 days in patients with high risk of hemorrhagic conversion

2014 AHA/ASA Stroke Guidelines

Mechanism of stroke with PFOMechanism of stroke with PFO

• Paradoxical embolism• Valsalva inducing activities?• Occult DVT?• ASA and thrombus? • Large PFO?• Atrial arrythmias?

• Paradoxical embolism• Valsalva inducing activities?• Occult DVT?• ASA and thrombus? • Large PFO?• Atrial arrythmias?

Mas et al. 2001

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WARCEF: HF with EF≤ 35%, no AF; 2305 patientsWARCEF: HF with EF≤ 35%, no AF; 2305 patients

NEJM 2012

• Significant reduction in the occurrence of ischemic stroke among patients on warfarin.

• This benefit was tempered by an increased risk of major hemorrhage in the warfarin group

Mitral stenosis: 1ary preventionMitral stenosis: 1ary prevention

Associated condition Treatment Class of Rec.

Prior embolic event Anticoagulation I, B

Left atrial thrombus Anticoagulation I, B

LA ≥55 mm Anticoagulation IIb, B

Large atrium, Spontaneousechocontrast

Anticoagulation IIb, C

AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014

Valve replacement: 1ary preventionValve replacement: 1ary prevention

Associated condition

Treatment Class of Rec.

Aortic, mechanical, no risk factors

Warfarin (2-3), aspirin I, B

Aortic, mechanical,risk factors

Warfarin (2.5-3.5), aspirin I, B

Mitral, mechanical Warfarin (2.5-3.5), aspirin I, B

Aortic, bioprosthetic AspirinWarfarin (2-3) for 3 months

IIa, BIIa, C

Mitral, bioprosthetic AspirinWarfarin (2-3) for 3 months

IIa, BIIa, C

AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014

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Other conditions: 1ary preventionOther conditions: 1ary preventionCondition Treatment Class of

Rec.

Myxoma Surgery I, C

Heart failure, no AF, no prior embolic event

Anticoagulant/antiplatelet

IIa, B

Fibroelastoma, symptomatic Surgery I, B

Fibroelastoma, asymptomatic,>1 cm , mobile

Surgery IIa, BIIa, C

LV thrombus post MI Anticoagulation IIa, C

LV aneurysm post MI Anticoagulation IIb, C

PFO, no prior stroke Antithrombotic/catheter therapy

III, C

AHA/ASA Guidelines for the primary prevention of stroke. Stroke 2014

Other conditions: 2ary preventionOther conditions: 2ary prevention

Condition Treatment Class of Rec.

Heart failure, LA or LV thrombus

Anticoagulation I, C

Heart failure, LVAD Anticoagulation IIa, C

LV thrombus post MI Anticoagulation IIa, C

LV aneurysm post MI Anticoagulation IIb, C

Aortic Arch Atheroma Antiplatelets I, A

Statins I, B

Anticoagulation IIb, C

Surgery III, C

AHA/ASA Guidelines for the secondary prevention of stroke. Stroke 2014

PFO: 2ary preventionPFO: 2ary prevention

Condition Treatment Class of Rec.

If no indication for OAC Antiplatelet I, B

DVT Anticoagulation I, A

DVT, Anticoagulation C/I IVC filter IIa, C

No DVT Closure III, A

DVT Closure IIb, C

AHA/ASA Guidelines for the secondary prevention of stroke. Stroke 2014

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• Multiple structural heart defects are associated with embolic stroke

• The diagnosis relies on detection of potential emboligenic sources in the absence of another etiology of equal or greater plausibility

• Imaging, including TEE is important• Treatment (medical/catheter

based/surgical) depends on the risk associated with the condition and requires a multidisciplinary approach

• Multiple structural heart defects are associated with embolic stroke

• The diagnosis relies on detection of potential emboligenic sources in the absence of another etiology of equal or greater plausibility

• Imaging, including TEE is important• Treatment (medical/catheter

based/surgical) depends on the risk associated with the condition and requires a multidisciplinary approach

ConclusionsConclusions

george.moukarbel@utoledo.edugeorge.moukarbel@utoledo.edu