Structural Heart Therapy to Treat Stroke

1. Structural Heart Therapy to Treat Stroke Atman P. Shah MD FACC FSCAI Director, Coronary Care Unit Co-Director, Structural Heart Therapies Assistant Professor of Medicine The University of Chicago

2. Novel Approaches • Background • The Role of PFO in stroke • Left Atrial Appendage occlusion • Conclusions

3. 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?

4. 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 Development of the atrial septum in utero Calvert, P. A. et al. (2011) Patent foramen ovale: anatomy, outcomes, and closure Nat. Rev. Cardiol. doi:10.1038/nrcardio.2010.224

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

8. Diagnosis • TTE Agitated Saline • Transcranial dopplers • Pts with detectable microemboli are more likely to have cerebral ischemia

9. 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

10. 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

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

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

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

17. 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

18. 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

19. 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

21. Left Atrial Appendage Closure

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

26. Warfarin for AFibLimitations Lead to Inadequate Treatment Adequacy of Anticoagulation inPatients with AFib in Primary Care Practice INR above target6% INR intarget range15% No warfarin65% Subtherapeutic INR 13% Samsa GP, et al. Arch Intern Med 2000;160:967.

27. 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.

28. 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

29. 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

31. 4 Steps

32. Access Delivery Capture Close Remove Echo Probe Appendage Heart Guide wire in sac 8.5f transseptal catheter Diaphragm

33. Access Delivery Capture Close Remove EndoCATHprepped & advanced over .025” FindrWIRE EndoCATH FindrWIRE Transseptal SofTIP Angiogram performed to visualize placement

34. Access Delivery Capture Close Remove FindrWIRZ EndoCATH FindrWIRZ Transseptal SofTIP SofTIP Transseptal EndoCATH w/ .025” FindrWIRZ .035” FindrWIRZ

35. Access Close Capture Delivery Remove Position snare at exclusion site using pre-determined reference EndoCATH LAA Snare Retract snare actuator completely FWZ Transseptal SofTIP

36. Access Close Capture Delivery Remove Exclusion location satisfactory? No Open snare and reposition Yes Move to “release of suture”

37. Access Delivery Capture Close Remove EndoCATH & .025” FindrWIRE removed

38. Access Delivery Capture Close Remove Before After Left Atrium Appendage Pericardium

39. Access Delivery Capture Close Remove 30 day TEE

40. Efficacy = Closed I PLACE II Safety & Efficacy Study II Closure defined as “complete” would =71%, Closure 3mm +/- 2mm * Retrospective analysis of Registry data - No closure data included **Closure = < 1mm

41. 41

42. 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  CENTER FOR VALVE DISEASE       Contact Us: 1-773-702-2500

43. Emerging Technology for the Treatment of Structural Heart Disease Special Thanks to: