Medtronic CoreValve ® System Summary of Clinical Experience UC201402534 EE

Medtronic CoreValve® System Summary of Clinical Experience

UC201402534 EE

INTERNATIONAL. CAUTION—For distribution only in markets where CoreValve has been approved. Not approved in the USA or Japan. ©Medtronic, Inc. 2013. All Rights Reserved. Non destiné au marché français.

• Background on aortic stenosis (AS) and introduction to transcatheter aortic valve implantation (TAVI)

• Overview of the CoreValve clinical portfolio

• CoreValve clinical performance– All-cause Survival– Efficacy– Other Outcomes

Agenda


Background• Aortic Stenosis (AS) is the most prevalent native valve disease1

• More than 300,000 patients have severe AS worldwide

• The mortality rate for untreated severe AS is up to 50%-60% within 2 years of the onset of severe symptoms

1Carabello BA, et al. Lancet 2009; 373:956-66


Treatment of Severe Aortic Stenosis

• Surgical aortic valve replacement (SAVR) is the gold standard for treatment of severe AS

• However, 33% of all patients ≥75 years of age with severe AS are declined for surgery1

• The mortality rate associated with SAVR increases substantially if certain comorbidities are present

– Left ventricular dysfunction

– Previous cardiac operations

– Chronic obstructive pulmonary disease

– Liver or renal failure

– Frailty1lung B, et al. Eur Heart J. 2005; 26(24):2714-2720


• Transcatheter aortic valve implantation (TAVI) is a viable treatment strategy for AS patients at high or extreme surgical risk

• TAVI has demonstrated significant survival improvements compared to medical management in inoperable patients in the PARTNER B trial1

• High risk patients receiving TAVI had similar survival rates to SAVR in the PARTNER A trial2

Treatment of Severe Aortic Stenosis

PARTNER B PARTNER A1Kapadia , et al., presented at TCT 2012 2Kodali S, et al., presented at ACC 2012


The Medtronic CoreValve System

• The Medtronic CoreValve® System has been implanted in more than 45,000 patients in more than 60 countries worldwide.

• Self-expanding nitinol frame• Tri-leaflet porcine pericardial tissue valve with supra-annular function• Four sizes (23, 26, 29, and 31 mm) to fit aortic annuli ranging from 18 to 29 mm • 18-Fr delivery catheter for all valve sizes• Delivery from a transfemoral, subclavian, or direct aortic approach


CoreValve® System Clinical ExperienceMedtronic CoreValve

Clinical Research Portfolio

Demonstrate Safety and Efficacy

Expand Access to New Populations and Markets

Confirm Efficacy and Optimize Practice


CoreValve® System Clinical ExperienceMedtronic CoreValve

Clinical Research Portfolio

References at end of presentation


CoreValve® System Clinical ExperienceNational CoreValve Registries

References at end of presentation


All-cause Survival


• When comparing all-cause survival across data sets, it is important to remember that many variables can influence a given rate.

• Baseline characteristics, patient selection practices, operator experience, complication management techniques, and in the case of registries, reporting practices, all play a role.

• Comparisons across data sets should be used to convey general trends, not to derive specific conclusions regarding TAVI devices.

All-cause Survival


1Chiam, et al., presented at EuroPCR 2013; 2Meredith, et al., presented at TCT 2012; 5Linke, et. al. presented at EuroPCR 2013 4Rueck, et al., presented at London Valves 2012; 5Tamburino, et al., Circulation 2011; 123: 299-308; 6Moat, et al. J Am Coll Cardiol 2011; 58(20): 2130-38; 7Godino, et al., J Am Coll Cardiol Intv 2010; 3: 1110-21; 8Avanzas, et al., Rev Esp Cardiol 2010; 63(2): 141-8; 9Bosmans, et al., ICVTS 2011; 12: 762-7; 10Gilard, et al. N Engl J Med 2012; 366: 1705-15

All-cause Survival │ 30-day National Registries and Medtronic Sponsored Studies

(independent studies, not head-to-head comparisons)

CoreValve


1Meredith, et al., presented at TCT 2012; 2Rueck, et al., presented at London Valves 2012; 3Tamburino, et al., Circulation 2011; 123: 299-308; 4Avanzas, et al., Rev Esp Cardiol 2010; 63(2): 141-8; 5Linke, et. al. presented at EuroPCR 2013; 6Bosmans, et al., ICVTS 2011; 12: 762-7; 7Moat, et al. J Am Coll Cardiol 2011; 58(20): 2130-38; 8Gilard, et al. N Engl J Med 2012; 366: 1705-15

All-cause Survival │ 1 Year National Registries and Medtronic Sponsored Studies


CoreValve


All-cause Survival │ 1 Year Rigorous Industry-Sponsored TAVI Studies


All routes

1Meredith, et. al. presented at TCT 2012; 2Linke, et. al. presented at EuroPCR 2013; 3Leon, et. al. presented at ACC 2013; 4Smith, et al. N Engl J Med 2011; 364: 2187-98; 5Leon, et al. N Engl J Med 2010; 363: 1597-1607


All-cause Survival │ 1 Year Select Contemporary Data Sets


All routes

1Meredith, et. al. presented at TCT 2012; 2Linke, et. al. presented at EuroPCR 2013; 3Windecker, et. al. presented at EuroPCR 2013; 4Leon, et. al. presented at ACC 2013; 5Smith, et al. N Engl J Med 2011; 364: 2187-98; 6Leon, et al. N Engl J Med 2010; 363: 1597-1607


All-cause Survival │ 1 YearNational Registries and Post-Market Approval Studies


1Tamburino, et al., Circulation 2011; 123: 299-308; 2Linke, et. al. presented at EuroPCR 2013; 3Windecker, et. al. presented at EuroPCR 2013; 4Moat, et al. J Am Coll Cardiol 2011; 58(20): 2130-38; 5Thomas, et al., presented at TCT 2012; 6Gilard, et al. N Engl J Med 2012; 366: 1705-15

All routes


The Italian registry1 and the Canadian registry2 have reported longer-term survival data on patient subsets

1Ussia, et al., Eur Heart J 2012; 33: 969-976; 2Rodes-Cabau, et al. J Am Coll Cardiol 2012; 60(19): 1864-75

All-cause Survival │ Longer-Term(independent studies, not head-to-head comparisons)


Efficacy• New York Heart Association (NYHA) Class status in the

ADVANCE study

• Health related quality of life (HRQoL) in the ADVANCE study

• Hemodynamics– 1-year CoreValve performance in the ADVANCE study– 3-year CoreValve performance in the Italian Registry


Efficacy │ New York Heart Association Class (NYHA)

The ADVANCE study demonstrated significant improvement in functional status at 1 month post-TAVI, which was sustained to 1 year

1Linke et al., presented at EuroPCR 2013


Efficacy │ Health Related Quality of Life6-month Outcomes from the ADVANCE Study

The ADVANCE study demonstrated significant improvements in post-TAVI quality of life using multiple measurement tools

1Bosmans, et al., presented at TCT 2012


1Linke, et al., presented at EuroPCR 2013

Hemodynamics │ CoreValve ADVANCE Study

The ADVANCE study has demonstrated that the CoreValve EOA and mean gradient remain stable out to 1 year


Hemodynamics │ Italian CoreValve Registry

1Ussia, et al., Eur Heart J 2012; 33: 969-76

The Italian Registry has demonstrated that the CoreValve EOA and mean gradient remain stable out to 3 years


Safety• Acute outcomes in the ADVANCE study

• Long term safety measures


Safety │ Acute OutcomesThe ADVANCE Study

The ADVANCE study shows that procedural complications are rare during CoreValve implants

1Linke, et al., presented at EuroPCR 2013


a Change in NYHA function resulting from intrinsic valve abnormality resulting in stenosis or regurgitation.

Safety │ Long-Term OutcomesMedtronic Foundational Studies

Two foundational CoreValve studies report no unexpected valve malfunctions or structural deterioration out to 4 years after implant

1Gerckens, et al., presented at EuroPCR 2011; 2Gerckens, et al., presented at ESC 2011


Procedural Success


Procedural SuccessNational Registries and Medtronic Sponsored Studies


CoreValve

1Chiam, et al., presented at EuroPCR 2013; 2Moat, et al. J Am Coll Cardiol 2011; 58(20): 2130-38; 3Meredith, et al., presented at TCT 2012; 4Avanzas, et al., Rev Esp Cardiol 2010; 63(2): 141-8; 5Bosmans, et al., ICVTS 2011; 12: 762-7; 6Gilard, et al. N Engl J Med 2012; 366: 1705-15; 7Linke, et. al. presented at EuroPCR 2013; 8Rueck, et al., presented at London Valves 2012; 9Tamburino, et al., Circulation 2011; 123: 299-308;


Major Vascular Complications• Definition

• Predictors

• Incidence


• According to VARC 1, Major Vascular Complications include all complications that can be caused by a wire and/or are related to vascular access, which lead to death, need for significant blood transfusions, unplanned intervention, or irreversible end-organ damage:

• The VARC 2 definition2 downgraded unplanned intervention during the index procedure to a minor vascular complication, except if it was associated with qualifying consequences.

VARC 1 Definition1

• Ventricular perforation• Aortic dissection or

rupture• Iliofemoral dissection

or rupture• Pseudoaneurysms• Closure failure

1Leon, et al., J Am Coll Card 2011; 57 (3): 253-69; 2Kappetein, et al., J Am Coll Cardiol 2012; 60: 1438-54

Major Vascular Complications │ Definition


• Femoral artery calcium score2, 4

• Female gender1

Patient-Related Factors

• Sheath to femoral artery ratio (SFAR)2

• Vessel tortuosity4

• Learning curve2

• Complication management3

• Percutaneous closure device failure5

• Patient selection3

Anatomical Factors Procedural Factors (Device / Operator)

1Genereux, et al. J Am Coll Cardiol 2012; 60(12): 1043-52; 2Hayashida, et al., J Am Coll Cardiol Cardiovasc Int 2011; 4(8): 851-8; 3Webb, et al., presented at TCT 2012; 4Vavuranakis, et al. Cardiovasc Ther 2013; epub; 5Cockburn, et al., Cath and Cardiovasc Interv 2012; 79: 143-49

Major Vascular Complications │ Predictors


Major Vascular Complications │ Predictors

1Van Mieghem, et al., Am J Cardiol 2012; 110(9): 1361-7

Effect of sheath size: the PRAGMATIC initiative showed patients treated with a 22F or 24F delivery sheath had significantly more vascular complications than

patients treated with smaller caliber devices(green bar represents Sapien, yellow is a mixture of Sapien XT and CoreValve)


1Fearon, et al., presented at ACC 2013; 2Hayashida, JACC Card Int 2011; 4(8): 851-8; 3Nuis, Am J Cardiol 2011; 107: 1824-1829; 4Toggweiler, JACC 2012; 59(2): 113-8

Effect of learning curve: four studies confirm that increased operator experience decreases the incidence of major vascular complications

Major Vascular Complications │ Predictors(independent studies, not head-to-head comparisons)


• Major vascular complication rate can be impacted by variables unrelated to the TAVI device (e.g., patient selection practices, operator experience and technique, complication management strategy, percutaneous closure device function, reporting practices in the case of registries).

• Examining outcomes over the wider clinical experience may lessen the impact of any one of these variables and provide a sense of TAVI device performance.

• However, it is important to be mindful that all of these factors do contribute to the incidence of major vascular complications and should be considered when doing incidence comparisons across studies.

Major Vascular Complications │ Incidence


1Linke, et al., presented at EuroPCR 2013; 2Gilard, et al. N Engl J Med 2012; 366: 1705-15; 3Meredith, et al., presented at TCT 2012; 4del Valle, et al., presented at London Valves 2012; 5Ussia, et al., presented at EuroPCR 2012

Major Vascular Complications │ IncidenceRegistry Data on CoreValve According to VARC 1



1Leon, et al., presented at ACC 2013; 2Fearon, et al., presented at ACC 2013; 3Sack, et al., presented at TCT 2012; 4Linke, et al., presented at EuroPCR 2013; 5Treede, et al., presented at EuroPCR 2013; 6Gilard, et al. N Engl J Med 2012; 366: 1705-15; 7Meredith, et al., presented at TCT 2012; 8del Valle, et al., presented at London Valves 2012; 9Ussia, et al., presented at EuroPCR 2012

Major Vascular Complications │ IncidenceSelect Data Sets Reporting According to VARC 1*



Aortic Regurgitation (AR)• Definition

• Predictors

• Incidence– Select Studies– CoreValve ADVANCE Study Outcomes

• Clinical Impact


• Aortic regurgitation (AR) can be transvalvular (central), paravalvular (PVL) or both.

Total AR = PVL + Transvalvular Leak

• What is clinically relevant is the total volume of flow through the valve

Image courtesy of Dr. J. Sinning, University of Bonn

Aortic Regurgitation │ Definition


• Calcified annulus (commissures, cusps, landing zone)3,4

• Male gender2,3

• Renal failure2

• Peripheral vascular disease1

• NYHA Class IV3


• LVOT-AO angle1

• Large annulus2

• Elliptical annulus3

• LVOT diameter5

• Transfemoral approach9

• Implant depth1,5,8

• Learning curve6

• Cover index (patient-prosthesis mismatch)4,5,6,7


1 Sherif, et al., J Am Coll Cardiol 2010; 56: 1623-9 ; 2Abdel-Wahab, et al., Heart 2011; 97: 899-906; 3Unbehaun, et al., J Am Coll Cardiol 2012; 59: 211-21; 4Gripari, et al., Heart 2012; 98: 1229-1236; 5Italy: Petronio, et al. The Italian CoreValve Registry. TCT 2012; 6Detaint, et al., J Am Colll Cardiol Intv 2009; 8: 821-7; 7Santos, et al., Eur H J Cardiovasc Img 2012; 13: 931-37; 8Chorianopoulos, et al., J Interven Cardiol 2012; 25: 174-179; 9Van Belle, et. al. Peri-valvular Aortic Regurgitation in Balloon-expendable and Self-expendable TAVI procedures: Predictors and Impact on clinical outcome - Insights from the FRANCE2 Registry; TCT 2012

Aortic Regurgitation │ Predictors


Effect of approach: FRANCE 21 and PARTNER2,3 demonstrate that the transfemoral approach (TF) results in approximately 50% more total AR

than the transapical (TA) approach

Aortic Regurgitation │ Predictors

1Van Belle, et. al., presented at TCT 2012; 2Kodali, et al., presented at TCT 2012;3Dewey, et. al., presented at TCT 2012;


Images of increasing levels of valve calcification1

Mechanism of PVL in calcified valves2

Aortic Regurgitation │ PredictorsEffect of calcification: heavy calcification may prevent perfect

apposition to the native annulus, increasing the risk of PVL

1John, et al., J Am Coll Cardiol Intv 2010; 3: 233-43; 2Sinning, et al, J Am Coll Cardiol 2012; 59: 1134-41


Mechanism of PVL in deep implant1

Mechanism of PVL in shallow implant1

Aortic Regurgitation │ PredictorsEffect of implant depth: appropriate implant depth minimizes potential flow

around the valve skirt. With CoreValve, a depth of 4-6 mm is currently recommended to minimize paravalvular leak.

1Sinning, et al, J Am Coll Cardiol 2012; 59: 1134-41; 2Tchetche, et al., EuroIntervention 2012; epub


CoreValve ADVANCE | Aortic Regurgitation


CoreValve ADVANCE | Paravalvular Leak


CoreValve ADVANCE | Transvalvular Regurgitation


• ASE / ESC guidelines, which are also recommended by VARC, are typically used to grade the severity of AR using echo. – NOTE: Until VARC 2, there was no consensus for measuring paravalvular leak in transcatheter

valves.

• Standardized criteria can be open to interpretation. It is important to verify that the severity grading criteria are the same when comparing AR across studies. – Is “mild” AR included in the study-specific definition of “significant” AR?

• In addition to the semi-quantitative nature of AR grading, intraobserver variability and variable baseline and procedural characteristics make it very difficult to do a robust comparison of AR across studies.

• Medtronic- and Edwards-sponsored TAVI studies apply similar echo criteria to grade the severity of AR, making it reasonable to compare the outcomes of these studies.

• It is difficult to draw strong conclusions about a TAVI device by doing cross-study comparisons.

Aortic Regurgitation │ Incidence


Aortic Regurgitation │ Incidence at 1 YearSelect Contemporary Data Sets


1Leon, et. al. presented at ACC 2013; 2Linke, et. al. presented at EuroPCR 2013; 3Leon, et al. N Engl J Med 2010; 363: 1597-1607; 4Smith, et al. N Engl J Med 2011; 364: 2187-98; 5Windecker, et. al. presented at EuroPCR 2013


Paravalvular Leak (PVL) │ Incidence at 1 YearSelect Contemporary Data Sets


1Leon, et. al. presented at ACC 2013; 2Linke, et. al. presented at EuroPCR 2013; 3Leon, et al. N Engl J Med 2010; 363: 1597-1607; 4Smith, et al. N Engl J Med 2011; 364: 2187-98; 5Windecker, et. al. presented at EuroPCR 2013


Paravalvular Leak (PVL) │ Incidence at 1 YearSelect Contemporary Data Sets—Transarterial Cohorts


1Leon, et. al. presented at ACC 2013; 2Kodali, et al., presented at TCT 2012; 3Linke, et. al. presented at EuroPCR 2013; 4Leon, et al. N Engl J Med 2010; 363: 1597-1607; 5Treede, et. al. presented at EuroPCR 2013


*At discharge

Aortic Regurgitation* │ Clinical ImpactMedtronic CoreValve ADVANCE Study

1Linke, et al. Presented at EuroPCR 2013


Stroke• Predictors

• Timing

• Incidence


• History of CABG1

• History of stroke3,5

• Coronary artery disease3

• Peripheral vascular disease5

• Baseline NYHA class3

• Chronic atrial fibrillation5

Late Stroke (30 days to 1 year after TAVI)

• Female gender1

• Surgical cutdown for access1

• New onset atrial fibrillation2

• Baseline aortic regurgitation 3+2

• Smaller aortic valve area3

• COPD4

• BMI <25 kg/m4

• Multiple implant attempts4

• Valve dislodgement5

• Balloon post-dilatation5

Early Stroke (within 30 days of TAVI)

1 Bosmans, et al., presented at EuroPCR 2013; 2Nuis, et al., Am J Cardiol 2012; 109: 1637-43; 3Miller, et al., J Thorac Cardiovasc Surg 2012;143(832-843): e13; 4Stortecky, et al., EuroIntervention 2012; 8: 62-70; 5Nombela-Franco, et al., Circulation 2012; 126(25): 3041-53

Stroke │ PredictorsRisk factors of early stroke tend to implicate embolization of annular debris,

while risk factors of late stroke point to comorbid conditions.


Stroke │ Type and Timing

The ADVANCE study showed that most strokes fall within 30 days of TAVI. However, due to their multi-morbid conditions, TAVI patients remain at risk for stroke long after

their procedure.

1 Bosmans, et al., presented at EuroPCR 2013

30-day Stroke Rate in ADVANCE: 3.0%


In the ADVANCE study, the overall stroke rate was low and remained relatively stable over time

Stroke │ Rate over Time

1 Bosmans, et al., presented at EuroPCR 2013


Multicenter registry data on 4,563 patients indicate that CoreValve has a historically low stroke rate, staying below 4.5% for any given cohort. It appears there is minimal learning

curve effect for this outcome.

Arrows indicate implant period and the reported rate of total stroke for the CoreValve cohort

Stroke │ Learning Curve


• Stroke rate is strongly impacted by patient comorbidities, and the timing of stroke events may indicate different mechanisms at play.

• When doing a comparison of stroke rate across studies, it is important to remember that the baseline patient characteristics can vary greatly.

• It is very difficult to draw conclusions about the performance of a particular TAVI device when comparing the incidence of stroke rate across studies.

Stroke │ Incidence


Stroke │ Incidence at 30 DaysSelect Data Sets


1Leon, et al. N Engl J Med 2010; 363: 1597-1607; 2Smith, et al. N Engl J Med 2011; 364: 2187-98; 3Thomas, et al., presented at TCT 2012; 4Leon, et al., presented at ACC 2013; 5Meredith, et al., presented at TCT 2012; 6Bosmans, et al., presented at EuroPCR 2013


Permanent Pacemaker Implantation (PPI)• Predictors

• Incidence

• Clinical Impact– Post-TAVI PPI– Post-TAVI Left Bundle Branch Block (LBBB)


• Right Bundle Branch Block (RBBB)2,3,4,5,7

• Other pre-existing conduction disturbances3,4,8,9

• Male gender3

• Age > 75 years9

• Previous MI3


• Variations in location of LBBB exit point1

• Septum thickness1,6

• Thickness of the non-coronary cusp1

• Implant Depth2,3,7

• Application of PPI guidelines10

• Learning Curve11

• Balloon Aortic Valvuloplasty8

• Radial force of the prosthesis3


More than 25 studies have been published on predictors of post-TAVI conduction disturbances (CDs) and permanent pacemaker implant (PPI)

1Jilaihawi, et al. Am Heart J 2009; 2Munoz-Garcıa, et. al. JACC CV 2012; 3Piazza et. al. EuroIntervention 2010; 4De Carlo , et. al. Am Heart J 2012; 5Calvi, et. al. JICE 2011; 6Saia, et. al. Cath Card Intv 2012; 7Fraccarao, et. al. Am J Card 2011; 8Khawaja, et. al. Circ 2011; 9Schroeter et. al. EuroPACE 2011; 10Wenaweser, et. al. presented at EuroPCR 2013; 11Meredith, et. al. presented at TCT 2012

Permanent Pacemaker Implantation │ Predictors


1Tchetche, et al. EuroIntervention 2012; 2Munoz-Garcıa, et. al. JACC CV 2012; 3Piazza et. al. EuroIntervention 2010; 4De Carlo , et. al. Am Heart J 2012; 5Calvi, et. al. JICE 2011; 6Saia, et. al. Cath Card Intv 2012; 7Fraccarao, et. al. Am J Card 2011; 8van der Boon, et. al. Int J Card 2013;

Effect of implant depth: data from independent studies plotted on the same graph show the strong relationship between PPI

rate and implant depth



PPM rates in 6-mo blocks of pt enrollment, except most recent is 8-mo.

Enrolling centers: 6 9 10 10 10 10 10 10

Effect of learning curve: the rate of PPI in the CoreValve Australia-New Zealand Study decreased over time as operators gained experience


1Muller, et al. Presented at EuroPCR 2013


Effect of PPI guideline use: varying 30-day pacemaker rates across geographies in the ADVANCE study may reflect

differences in the application of PPI guidelines

Countries with less than 15 implants not shown


1Wenaweser, et al. Presented at EuroPCR 2013


• The permanent pacemaker implantation rate can be impacted by variables unrelated to the TAVI device (e.g., baseline conduction disturbances, anatomical differences, clinician preference for prophylactic pacemaker use, and operator experience).

• These factors should be kept in mind when comparing the incidence of permanent pacemaker implantation across studies.

Permanent Pacemaker Implantation │ Incidence


1Chiam, et al., presented at EuroPCR 2013; 2Tamburino, et al., Circulation 2011; 123: 299-308; 3Brito, et.al., presented at TCT 2011; 4Gilard, et al. N Engl J Med 2012; 366: 1705-15; 5Moat, et al., J Am Coll Cardiol 2011; 58(20): 2130-38; 6del Valle, et al., presented at London Valves 2012; 7Wenaweser, et al., presented at EuroPCR 2013; 8Muller, et al., presented at EuroPCR 2013

Permanent Pacemaker Implantation │ IncidenceCoreValve Outcomes in National Registries and Studies



Both the ADVANCE study1 and the Australia-New Zealand Study2 showed no impact of a new permanent pacemaker implant on mortality

1Wenaweser, et al. Presented at EuroPCR 2013; 2Muller, et al. Presented at EuroPCR 2013

Permanent Pacemaker Implant │ Clinical Impact


LBBB Post-TAVI NO Mortality Impact

Houthuizen, et. al. Circulation 2012, (N=679)

Urena, et. al. JACC 2012, (N=202)

De Carlo, et. al. AHJ 2012, (N=275)

LBBB Post-TAVI Mortality Impact

Patients not receiving permanent pacemaker before discharge.

Muller, et. al. EuroPCR 2013, (N=200)

Current Research is Inconclusive Regarding Mortality Impact of LBBB Post –TAVI

Left Bundle Branch Block │ Clinical Impact


Both the ADVANCE study1 and PARTNER2 showed no impact of a new LBBB on mortality


1Wenaweser, et al. Presented at EuroPCR 2013; 2Nazif, et al. Presented at ACC 2013


Both the ADVANCE study1 and the Australia-New Zealand Study2 showed no significant adverse effect of a new LBBB at discharge on

the mean LV ejection fraction

1Wenaweser, et al. Presented at EuroPCR 2013; 2Muller, et al. Presented at EuroPCR 2013



References for slides 8, 9, and 541. ClinicalTrials.gov Identifier: NCT012409022. Buellesfeld L, et al. J Am Coll Cardiol 2011; 57: 1650-7.3. ClinicalTrials.gov Identifier: NCT01586910 4. ClinicalTrials.gov Identifier: NCT016754405. Meredith IT, et al. Presented at TCT 20126. Medtronic CoreValve Japan Trial, protocol MDT-21117. ClinicalTrials.gov Identifier: NCT015313748. Linke A, et al. Presented at EuroPCR 2013.9. ClinicalTrials.gov Identifier: NCT0162487010. ClinicalTrials.gov Identifier: NCT0167672711. France II Registry. Eltchaninoff H, Presented at TVT 201312. Italian Registry. Ussia GP, et al. Presented at EuroPCR 201213. Italian Registry. Petronio AS, et al., Presented at TCT 2012.14. Israel Registry. Kornowski R, et al. Presented at EuroPCR 2012.15. UK Registry. Moat NE, et al. J Am Coll Cardiol 2011; 58: 2130-8.16. UK Registry. Moat NE, et al. Presented at TCT 2012.17. Belgian Registry. Bosmans J, et al. Presented at EuroPCR 201218. Bosmans J, et al., Interact Cardiovasc Thorac Surg 2011; 12(5): 762-7.19. Brazilian Registry. Brito FS, et al. Presented at TCT 2011.20. Spanish Registry. Avanzas P, et al., Rev Esp Cardiol. 2010;63:141-8.21. Milan Registry. Buchanan GL, et al. Presented at EuroPCR 2012.22. Asia Registry. Chiam P, Presented at EuroPCR 2013.23. del Valle R, et al., Presented at PCR London Valves 201224. Ruck A, et al., Presented at PCR London Valves 201225. Figulla H, et al., Presented at TCT 201226. GARY, Mohr F, Presented at ACC 201327. German TAVI Registry: Sinning, et al., Am Heart J 2012; 164: 102-110.e1

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Medtronic CoreValve ® System Summary of Clinical Experience UC201402534 EE