Structural Heart Therapy to Treat Stroke

Structural Heart Therapy to Treat Stroke

Atman P. Shah MD FACC FSCAIDirector, Coronary Care Unit

Co-Director, Structural Heart TherapiesAssistant Professor of Medicine

The University of Chicago

Novel Approaches

• Background• The Role of PFO in stroke• Left Atrial Appendage occlusion• Conclusions

PFO

• Patent foramen ovale (PFO) is a normal fetal communication between the right and left atria that persists postpartum

• PFOs are present in 20–34% of the population• PFOs can open and act as a conduit for thrombi to pass

from the systemic venous circulation to the systemic arterial circulation, which can potentially cause a stroke

• PFOs have been associated with cryptogenic stroke, decompression illness, systemic arterial embolism, and migraine with aura

• Closure is low risk, but is there data to do so?

Development of the atrial septum in utero

Calvert, P. A. et al. (2011) Patent foramen ovale: anatomy, outcomes, and closureNat. Rev. Cardiol. doi:10.1038/nrcardio.2010.224

a | The septum primum grows from the roof of the atria.

b | Fenestrations develop within the septum primum.

c | The septum secundum develops by an infolding of the atrial walls. The ostium secundum acts as a conduit for right-to-left shunting of oxygenated blood.

d | At the anterosuperior edge of the fossa ovalis, the primum and secundum septa remain unfused, which constitutes a PFO

Schematic representation of the atrial septal anatomy from an en-face view of the right atrium

Diagnosis

• TTE Agitated Saline• Transcranial dopplers

– Pts with detectable microemboli are more likely to have cerebral ischemia

ASA and Chiari• Atrial Septal aneurysm (ASA) has been defined

as a total movement of the septum primum from the left to the right atria of >10 mm

• Lies within the septum primum and can result in a large R-L shunt and may undermine stability of a closure device

• A eustachian valve (valve of the inferior vena cava) or a Chiari network are both embryological remnants of the right valve of the sinus venosus

• Both of these structures direct blood flow from the inferior vena cava towards the right atrial opening of the PFO and can interfere with deployment of the right atrial disc of an occluder or with the retrieval of a closure device

Cryptogenic Stroke• Stroke of unknown

cause, despite extensive investigation to exclude other causes

• Paradoxical embolus initially used to describe a branched thrombus from a uterine vein

• Presence of DVT was more common in patients with cryptogenic stroke

• Large PFO with ASA results in “afib-like” left atrial physiology

Cramer Stroke 2004

Windecker JACC 2004• 308 patients with PFO and with CVA/TIA were randomized to medical therapy or

closure

Calvert, P. A. et al. (2011) Patent foramen ovale: anatomy, outcomes, and closureNat. Rev. Cardiol. doi:10.1038/nrcardio.2010.224

Calvert, P. A. et al. (2011) Patent foramen ovale: anatomy, outcomes, and closureNat. Rev. Cardiol. doi:10.1038/nrcardio.2010.224

High Risk Features?

• Size of PFO, the separation between primum and secundum

• Degre of shunt, count of microbubbles• Role of a prominent Eustachian valve• Increased right sided pressure states• DVT• Prothrombotic states

Homma J Cardiol 2010

CLOSURE (or not really)

• 909 patients randomized to NMT or Med Rx• No difference in primary endpoint (5.5% vs

7.7%) stroke/TIA at 2 years• 90% successful implant• Higher afib rate in NMT group (5.7% vs 0.7%;

p<0.001)• CLOSE (open label), PC-Trial (closure vs. pmed

regiments), GORE REDUCE trial• RESPECT stopped enrollment

Whom to Close?

• Young patients with high risk anatomic features who have had a stroke

• Older patients may also benefit, but may need TCDs to truly document potential CNS complications

Left Atrial Appendage Closure

Go et al. JAMA 2001;285:2370-5

Warfarin for AFib Limitations Lead to Inadequate Treatment

Samsa GP, et al. Arch Intern Med 2000;160:967.

INR above targetINR above target6%6%

Subtherapeutic INR Subtherapeutic INR 13%13%

INR inINR intarget rangetarget range

15%15%No warfarinNo warfarin

65%65%

Adequacy of Anticoagulation inPatients with AFib in Primary Care Practice

PLAATO• 180 patients with non-rheumatic atrial fibrillation and contraindication to

warfarin therapy

• ?history of transient ischaemic attack (TIA) or stroke or at least two independent risk factors for stroke such as age > or =75 years, hypertension, congestive heart failure or diabetes.

• The primary endpoint was LAA closure as determined by TEE two months after the procedure and stroke rate at 150 patient years.

• Left atrial appendage occlusion was successful in 162/180 patients (90%, 95% CI 83.1% to 92.9%).

• Two patients died within 24 hours of the procedure (1.1%, 95% CI 0.3% to 4%). Six cardiac tamponades were observed (3.3%, 95% CI 1.5% to 7.1%).

• 90% successful occlusion of the LAA

• Expected incidence of stroke according to the CHADS2-Score was 6.6% per year.

• The trial was halted prematurely during the follow-up phase for financial considerations.

PROTECT AF

• In 707 patients, associated with a 38% reduction in endpoint (stroke CV Death, and systemic embolism)

• Successfully implanted in 91% of patients

• 87% of patients were able to d/c warfarin after 45 days

• Increased procedural risk, but that decreased with experience

Sizes 21mm-33mm delivered via a 12French system

• PROTECT 2 trial was noninferior in the composite endpoint (stroke, cardiovascular death, systemic embolism)

• Higher rates of serious pericardial effusion, embolization, and procedure related stroke

Holmes Lancet 2009

4 Steps

AccessAccess DeliveryDelivery CaptureCapture CloseClose RemoveRemove

Appendage

Echo Probe

Guide wire in sac

8.5f transseptal catheter

Heart

Diaphragm

EndoCATH prepped &

advanced over.025” FindrWIRE

Angiogram performed to visualize placement

AccessAccess DeliveryDelivery CaptureCapture CloseClose RemoveRemove

SofTIPSofTIP

EndoCATHEndoCATH

FindrWIREFindrWIRE

TransseptalTransseptal

AccessAccess DeliveryDelivery CaptureCapture CloseClose RemoveRemove

FindrWIRZFindrWIRZ

SofTIPSofTIP

EndoCATHEndoCATH

FindrWIRZFindrWIRZ

TransseptalTransseptal

SofTIPSofTIP

.035” .035” FindrWIRZFindrWIRZ

TransseptalTransseptalEndoCATH EndoCATH

w/ .025”w/ .025”FindrWIRZFindrWIRZ

AccessAccess CloseClose RemoveRemoveCaptureCaptureDeliveryDelivery

Position snare at exclusion site using pre-determined reference

Retract snare actuator completelyLAALAASnareSnare

SofTIPSofTIP

FWZFWZ

EndoCATHEndoCATH

TransseptalTransseptal

AccessAccess CloseClose RemoveRemoveCaptureCapture

Exclusion location satisfactory?

NoOpen snare and reposition

YesMove to “release of suture”

DeliveryDelivery

AccessAccess DeliveryDelivery CaptureCapture CloseClose

EndoCATH & .025” FindrWIRE removed

RemoveRemove

AccessAccess RemoveRemoveDeliveryDelivery CaptureCapture CloseClose

Before After

Left Atrium

Appendage

Pericardium

AccessAccess DeliveryDelivery CaptureCapture CloseClose RemoveRemove

30 day TEE

Efficacy = Closed

PLACEPLACE II Study

# Pts 99

Intent-to-Treat 95/99 (96%)

Acute Closure 97/99 (98%)

>30d Closure 82/85** (97%)

Access Requirement

8.5F SL1

II Closure defined as “complete” would =71%, Closure 3mm +/- 2mmI PLACE II Safety & Efficacy Study* Retrospective analysis of Registry data - No closure data included

WATCHMANPROTECT AF TrialII

463

408/463 (88%)

NA

346/408 (85%)1I

14F

**Closure = < 1mm

4141

Conclusions

• Recent advances have resulted in new opportunities to reduce stroke

• Devices to reduce stroke are improving and afford the practitioner an important tool to help patients

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