Columbia University Medical Center Cardiovascular Research Foundation Will Vascular Complications Remain the Achilles’ Heel of Transfemoral TAVI? – Cardiology View Martin B. Leon, MD Columbia University Medical Center Cardiovascular Research Foundation New York City CRT 2011; Washington DC February 27- March 1, 2011

Presenter Disclosure Information for CRT Symposium; February 28, 2011 Martin B. Leon, M.D. NON-PAID Consultant: Edwards Lifesciences, Medtronic Consultant: Symetis Equity Relationship: Claret, Sadra, Vivasure

Vascular Complications - TAVI Background

REVIVE & REVIVAL Vascular Complications (15.5%) Perforations (n=12) Covered Stent - 3 3 Deaths Surgical Bypass - 9 Flow Limiting Iliac Dissection (n=4) 2 Deaths Surgical Repair - 4 In Hospital Mortality in Patients with a Vascular Complication – 36% In Hospital Mortality in Patients without a Vascular Complication – 10.3% Vascular Complications (n=25) Avulsed Iliac Artery (n=3) Surgical Bypass - 3 Aortic Dissection (n=3) Surgery - 1 2 Deaths Medical - 2 Lower Extremity Ischemia (n=4) Surgery - 2 2 Deaths Medical - 2 3 3

Edwards TAVI Complications Multiple Data Sources (TA and TF) POOLED* (503 pts) SOURCE (1038 pts) VANCOUVER (250 pts) PARIS (75 pts) CA-Multictr (339 pts) Vascular (maj)** (%) 18.5 10.6 10.3 11.8 13.1 AR >2+ (%) 10.9 4.7 5.0 5.3 7.7 Stroke (%) 4.0 2.5 3.0 2.3 New Pacemaker (%) 4.4 7.0 5.5 4.9 Renal Failure (%) 5.2 8.7 4.2 na 2.6 Coronary Obstr (%) 0.6 * REVIVE, REVIVAL, TRAVERCE, PARTNER EU ** TF Only

SOURCE Vascular Complications 1-Year Survival (22/24F Device) Approach % Survival in Pts who did not have vascular complications % Survival in Pts who did have vascular complications P-Value TF 83.9% 72.2% 0.0121 Without Vascular Complication With Vascular Complication Survival Months post Procedure 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 1 2 3 4 5 6 7 8 9 10 11 12 Trans-femoral (463 pts) 5 5

Published on-line September 22, 2010 @ NEJM Published on-line September 22, 2010 @ NEJM.org and print October 21, 2010 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) On behalf of the Executive Committee, the Investigator Sites, and the courageous patients who participated in the PARTNER trial! 6

VARC Definitions J Am Coll Cardiol 2011; 67:253-69 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) J Am Coll Cardiol 2011; 67:253-69 7

Clinical Outcomes at 30 Days and 1 Year Vascular Complications Major All P<0.0001 P<0.0001 per cent P<0.0001 P<0.0001 TAVI (n=179) Standard Rx (n=179)

Mortality vs. Major Vasc Complics TAVI patients Major Vascular Complication (n=31) No Major Vascular Complication (n=148) P (log rank) = 0.069 47.2% Mortality (%) 27.7% Months 9

Vascular Complications - TAVI Solutions

Vascular Complications - TAVI Solutions Smaller profile sheaths (and new expandable sheath systems)

Edwards TAVI Sheaths Delivery Systems are Improving 24F 22F 18F

Vascular Complications - TAVI Solutions Smaller profile sheaths (and new expandable sheath systems) Meticulous vascular screening and team training

TAVI Vascular Access Screening All patients - angiogram and CTA or IVUS/non-contrast CT if renal function a concern. Contrast requiring procedures are separated Diagnostic cath performed non-Rx side Studies carefully reviewed by entire team with focus on vessel size, tortuousity, pathology and calcification (especially at bifurcations)

TAVI Vascular Access Assessment (trans-femoral) Vessel Size Determined with CTA or IVUS Avoid use of angiogram as sole method Tortuosity Determined with angiogram During diagnostic place stiff wire to determine ability of artery to ‘straighten’ Calcification Determine with non-contrast, non-subtracted cine and non-contrast CT Greatest concern is circumferential calcification at bifurcations (location is critical) Lesions Severity, focal vs. diffuse, +/- calcified, location

REVIVE improved screening to reduce vascular complications Vascular Access Complication Rate, by patient January 2006 – June 2006 30% Vascular Access Complication Rate, by patient August 2006 – December 2007 5.8% Vascular Screening with Columbia University Medical Center Core Lab INSTITUTED (in coordination with DSMB) P = .006 16 16

Vascular Complications - TAVI Solutions Smaller profile sheaths (and new expandable sheath systems) Meticulous vascular screening and team training Liberal use of alternative vascular access sites (don’t push the envelope)

TAVI Vascular Access Sites Trans - femoral Most common; limited by local anatomy/pathology Only percutaneous access and closure site Trans - apical Mini-thoracotomy; requires more training Trans - subclavian/axillary Alternative if femoral inaccessible Trans - iliac/abdominal aorta Retro-peritoneal surgical access + conduit Trans - thoracic aorta Mini-thoracotomy alternative This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 18

Vascular Complications - TAVI Solutions Smaller profile sheaths (and new expandable sheath systems) Meticulous vascular screening and team training Liberal use of alternative vascular access sites (don’t push the envelope) Percutaneous access and closure (and new dedicated closure devices in the future)

TAVI Vascular Closure Techniques (trans-femoral) PERCUTANEOUS CLOSURE – Why? Simplifies the procedure and facilitates use of conscious sedation Improves patient comfort and facilitates early ambulation (and discharge) Becomes comprehensive interventional non-surgical procedure – less dependence on OR environment, anesthesia, and surgeons

TAVI Vascular Closure Techniques (trans-femoral) PERCUTANEOUS CLOSURE Suture mediated One Prostar Two (or three) Proglides Other devices under development

Columbia CBOT after TAVI 58 Transfemoral TAVIs (November 2008 to September 2010) Columbia CBOT after TAVI 2 Elective Surgical Repairs (Vessel unsuitable for percutaneous closure) 56 Percutaneous closure with CBOT 95% Success Rate 3 (5.4%) Failed closure/Bridge to Surgical Repair 1 occlusive dissection of external iliac 2 perforation of external iliac 53 (94.6%) Successful Closures 24 (42.8%) Primary Closure 29 (51.8%) Therapeutic CBOTs 26 (46.4%) Post-dilatation Balloon only 3 (5.4%) Endovascular Stent

Vascular Complications - TAVI An Ongoing Achilles’ Heel? As with most things in interventional cardiology, the combination of 1) improved technology (lower profiles and dedicated closure devices), 2) meticulous training, screening and procedure planning, and 3) evolving operator experience – will significantly reduce the frequency and severity of TAVI-related vascular complications, maintaining the transfemoral approach as the dominant access strategy in the future!