Actor Portrayal

SYMPTOMATICAORTIC STENOSISTIMING IS EVERYTHING

Urgent referral can save lives

2

THE URGENCYAortic stenosis (AS) is among the most common of all valvular heart diseases in Europe and continues to increase as the population ages.1

For patients, AS often goes unnoticed. Once they begin to feel symptoms, their condition can be fatal if left untreated.

350,000 people in Western Europe develop symptomatic severe aortic stenosis (SSAS) annually.2-10

MEDICAL MANAGEMENTISN’T ENOUGHAfter developing severe aortic stenosis (SAS), the average patient survival is two years without treatment.11

100%

80%

60%

40%

20%

0%400 50 60 70 80

Surv

ival

(%)

Age (Years)

Onset SevereSymptoms

Latent Period

Increasing obstruction,myocardial overload

0 2 4 6AverageSurvival, Years

ANGINASYNCOPEFAILURE

Approximately

Actor Portrayal

3

* Above 65 years3

EARLY DIAGNOSIS AND TREATMENT CAN MEAN BETTER OUTCOMESSymptomatic severe aortic stenosis isn’t always easy to diagnose because:

§ Heart murmurs go undetected.12

§ Referrals are delayed or too late.12

§ Echocardiogram findings are misclassified due to complex cardiac anatomy.12

§ Patients don’t recognize or report their symptoms.13

§ Patients refuse treatment.11

MORE THAN A THIRD OF THE ELDERLY POPULATION* HAVE UNDIAGNOSED AORTIC VALVE DISEASE.14

DELAYED VALVE INTERVENTION CAN NEGATIVELY IMPACT TREATMENT OUTCOMES.15

4

MIND THEMURMURYou can help save more lives by recognizing the symptoms of symptomatic severe aortic stenosis (SSAS) early on.

TIMING IS EVERYTHING FOR SYMPTOMATIC AORTIC STENOSIS PATIENTS

REMEMBER TO:

Listen for the murmur.

Order an echocardiogram.

Refer patients to a heart valve team without delay.

1

2

3

5

PATIENTS RELY ON YOUREXPERTISEPatients look to you for answers. Advise your symptomatic severe aortic stenosis (SSAS) patients to seek an evaluation by the heart team without delay.

are influenced by conversations with their doctor when making SSAS treatment decisions.16

OF PATIENTS WITH HEART VALVE DISEASE 90%

Actor Portrayal

6

FOLLOW ESC/EACTS GUIDELINESIntervention is indicated in symptomatic patients with:17

Severe, high-gradient aortic stenosis

§ Aortic valve area (AVA) <1 cm2 AND mean gradient ≥40 mmHg or peak velocity ≥4.0 m/s

§ Non-reversible high flow status with gradient AS also considered severe

CLASS I

LEVEL B

CLASS I

LEVEL C

Severe, low-flow, low-gradient aortic stenosis with reduced ejection fraction and evidence of flow (contractile) reserve excluding pseudosevere aortic stenosis.

§ AVA <1 cm2 AND mean gradient <40 mmHg AND peak velocity <4.0 m/s

§ Reduced ejection fraction <50% Stroke Volume index (SVi) ≤35 mL/m2

§ Dobutamine Echo with evidence of flow reserve excluding pseudosevere aortic stenosis

Decision making for intervention should be made by a ‘Heart Team’ with a particular expertise in VHD, comprising cardiologists, cardiac surgeons, imaging specialists, anaesthetists and, if needed, general practitioners, geriatricians and heart failure, electrophysiology or intensive care specialists.

ESC/EACTS Valvular Heart Disease Guidelines17

7

MANAGEMENT OF SEVERE AORTIC STENOSIS

AS = Aortic Stenosis

LVEF = Left Ventricular Ejection Fraction

SAVR = Surgical Aortic Valve Replacement

TAVI = Transcatheter Aortic Valve Implantation.

a Surgery should be considered (IIa C) if one of the following is present: peak velocity >5.5 m/s; severe valve calcification + peak velocity progression ≥0.3m/s per year; markedly elevated neurohormones (>threefold age-and sex-corrected normal range) without other explanation; severe pulmonary hypertension (systolic pulmonary artery pressure >60 mmHg).

b See tables of recommendation in ESC/EACTS guidelines published here: https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Valvular-Heart-Disease-Management-of

Does the patient exhibit symptoms?

LVEF <50%

Physically active

Presence of risk factorsa and low individual surgical risk

SAVRRe-evaluate in 6 months

or when symptoms occurSAVR or TAVI

Exercise test

Medical therapy

Symptoms or fall in blood pressure below baseline

Careful individual evaluation of technical

stability and risk-benefit ratio of intervention

modes by the Heart Team

Absence of comorbidity or general condition that make benefit unlikely

Low risk and no other characteristics that favor TAVIb

No

No

No

No

Yes

Yes

Yes Yes

No

No

No

Yes

Yes

Yes

Yes

From the 2017 ESC/EACTS guidelines for the management of valvular heart disease17

8

AORTIC VALVE REPLACEMENT GREATLY IMPROVES THE RATE OF SURVIVAL18

Years

OperatedUnoperated

OperatedUnoperated

Chi2 = 23.5p < 0.001

< 0.05 < 0.001

100

80

60

40

20

00 1 2 3 4 5

Surv

ival

(%)

125 8719 8

512

351

90

05

Mortality difference for people with symptoms of aortic stenosis treated with aortic valve replacement versus those not undergoing this procedure is one of the most striking in medicine.18

Actor Portrayal

Actor Portrayal9

“ Aortic valve replacement improves physical quality of life, general health, and vitality in patients with symptomatic severe aortic stenosis.”19

10

MORE SEVERE AORTIC STENOSISPATIENTSCAN BE TREATEDWith indication expansion for the Evolut™ TAVI procedure to include low risk* and severe bicuspid** aortic stenosis patients, you have new opportunities to offer your patients the less-invasive TAVI treatment option.

*Patients ≥70 years of age with an LVEF >30%.**Patients who are at intermediate or greater risk for SAVR.

IntermediateRisk

Indicated for:TAVI

Low RiskHigh Risk

ExtremeRisk

17%

28%

24%

31%

Distribution of incidence by surgical risk2-10

11

11

EVOLUT™ TAVI PLATFORMMEANINGFULINNOVATIONDRIVING BETTER OUTCOMES

Powered by our unwavering mission to alleviate pain, restore health, and extend life, we are developing innovative technologies and solutions to benefit patients and healthcare systems across the world. We continuously challenge ourselves and our clinical partnerships to bring innovative products, services, and technologies to the market without compromising quality.

Evolut™ TAVI Platform

CoreValve™

2007

2021

an

d be

yond

Evolut™ R Evolut™ PRO Evolut™ PRO+

Rapid, meaningful innovation

12

EVOLUT™ PRO+ SYSTEM EXCEPTIONAL DESIGN

THE EVOLUT TAVI PLATFORMA proven, supra-annular, self-expanding Evolut TAVI platform.22

HEMODYNAMIC PERFORMANCE

LOW DELIVERY PROFILE

LOW PVL RATES

RECAPTURABILITY

ENGINEERED FOR TODAY AND TOMORROW

The supra-annular design keeps the working portion of the valve above, and unconstrained.

Self-expanding nitinol frame provides a compact design and low delivery profile.

Low delivery profile The Evolut™ PRO+ valve provides a low delivery profile and added surface area contact between the valve and the native aortic annulus to further advance valve sealing performance.21

The delivery system assists in positioning and repositioning of the valve allowing for the valve to be implanted and adjusted more accurately.*

Hemodynamic performance for exceptional patient outcomes20

Advanced sealing for all valve sizes and across the broadest self-expanding annular range†

† Broadest annulus range based on CT derived diameters for self-expanding valves* Deployment of the same valve can be attempted max. 3 times.

Actor Portrayal

Evolut™ TAVI Platform

13

Clinical benefits of a large effective orifice area (EOA):

§ Means less workload for the ventricle.23

§ Helps avoid patient-prosthesis mismatch (PPM).24

§ Provides improved flow, less resistance, and suggests benefits to long-term durability.25,26

2.3 cm2

AVERAGE EOA AT 1 YEAR20

EFFECTIVE ORIFICE AREA MATTERS

Patient-prosthesis mismatch (PPM): PPM occurs when the effective orifice area of the implanted prosthetic valve is too small in relation to the patient's body size. This drives gradients higher, particularly during exercise.27,28 Severe PPM has been associated with increased mortality.29

14

Evolut™ TAVI is the only TAVI device to demonstrate hemodynamic superiority in a Low Risk Trial vs. SAVR at one year.20

23%

SUPERIOR EOAs at 1 year

EVOLUT TAVI 2.3 cm2 vs. SAVR 2.0 cm2

SUPERIOR Gradients at 1 year

EVOLUT TAVI 8.6 mm Hg vs. SAVR 11.2 mm Hg

15%

LOWER GRADIENTSLARGER EOAs

EVOLUT™ TAVI SUPERIOR HEMODYNAMICS

Evolut™ TAVI Platform

15

15

BETTER PATIENT OUTCOMES

45%fewer deaths, disabling strokes and heart failure rehospitalizations for Evolut™ TAVI compared to SAVR in the Evolut Low Risk Trial.30

Esti

mat

ed K

M R

ates

(%)

0

2%

4%

6%

12%

SAVRTAVI

8%

10%

3.1

2.3

0.7

3.0

2.3

6.4 Composite Rate

TAVI5.6%

SAVR10.2%

HF HospitalizationDisabling StrokeDeath

Difference = -4.5%P = 0.002

1 Year (%)

16

Evolut™ TAVI consistently demonstrates stable EOAs and gradients across various robust clinical studies.20,31 Stable hemodynamics are a well-known signal for valve durability.32

EVOLUT™ TAVI CONSISTENT HEMODYNAMICS

0.6

1.8 1.9 1.8 1.9 1.9

48.2

8.9 7.8 9.1 7.8 8.3

0.0

10.0

20.0

30.0

40.0

50.0

60.0

Baseline 1-7 Days 30 Days 1 Year 2 Years 3 Years0.0

0.5

1.0

1.5

2.0

2.5 Effective orifice areaMean gradient

Effec

tive

Ori

fice

Are

a, c

m2

Mean G

radient, mm

Hg

Gradient 237 222 223 185 154 129

EOA 211 198 205 160 139 114

Baseline 1 Mo 6 Mo 12 Mo 24 Mo0.0

0.5

1.0

1.5

2.0

2.5

3.0 TAVISAVR

0.0

10.0

20.0

30.0

40.0

50.0

60.0

0.8

2.2 2.22.3

2.2

0.9

2.0 2.0 2.0 2.0

44.8

8.4 8.7 8.6 9.0

44.2

10.5 11.2 11.2 12.3

Aortic Valve Area, cm

2

AV Mean G

radient, mm Hg

Implanted population. Core lab assessments. 

TAVI Statistically Superior At All Time Points

Evolut R Hemodynamics31 Evolut ValveHemodynamics in Low Risk Patients30

Evolut™ TAVI Platform hemodynamically outperforms surgical valves in low risk patients at all evaluated timepoints.30

EOA = Effective orifice area

17

Evolut™ TAVI consistently demonstrates stable EOAs and gradients across various robust clinical studies.20,31 Stable hemodynamics are a well-known signal for valve durability.32

THE HEMODYNAMIC PERFORMANCE OF THE SUPRA-ANNULAR TAVI PLATFORMLONG-TERM DATA

0

20

40

60

0 1 2 3

Years

SVD

(%)

SAVRTAVI

P = 0.001

4 5 6 7 8

10

30

50

70

28.5%

14.1%

SAVRTAVI

135139

113130

105126

97115

84107

7594

6280

5468

3044

NOTION TRIAL8-Year Data on the CoreValve™ TAV33

In a recent update on patients at lower surgical risk over the age of 70, we continue to see stastically better hemodynamics versus surgery – as well as a promising signal of durability.

Findings From 8-Year Follow-Up on the CoreValve™ TAV33

§ Hemodynamics were statistically better versus surgery out to 8 years.

§ Structural valve deterioration (SVD) was statistically better than surgery out to 8 years.

Structural valve deterioration32

§ Moderate or greater hemodynamic SVD

§ Mean gradient ≥ 20mm Hg or

§ Mean gradient ≥ 10 mm Hg change from baseline or

§ Moderate/severe intra-prosthetic aortic regurgitation (AR) (new or worsening from baseline)

Half the Rate of SVD Versus Surgery33

SVD out to 8 years

18

*Patients ≥70 years of age with an LVEF >30%

** Evolut™ TAVI Platform is indicated for treatment of patients with severe bicuspid aortic stenosis who are at intermediate or greater risk for SAVR

EVOLUT™ R/PRO/PRO+

EXTREME RISK

HIGH RISK

INTERMEDIATE RISK

LOW RISK*

TAV IN SAV

BICUSPID**

TAVI - PLATFORM

INDICATIONS

EVOLUT™ TAVI PLATFORM CE MARKED INDICATIONS FOR PATIENTS WITH SEVERE AORTIC STENOSIS

19

References 1 Carabello BA, Paulus WJ. Aortic stenosis. Lancet. March 14, 2009;373(9667):956-966. 2 STS Adult Cardiac Database. 2010 Harvest, Isolated AVR. 3 Bach DS, Cimino N, Deeb GM. Unoperated patients with severe aortic stenosis. J Am Coll

Cardiol. November 13, 2007;50(20):2018-2019. 4 Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic,

hemodynamically significant aortic stenosis during prolonged follow-up. Circulation. June 21, 2005;111(24):3290-3295.

5 Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis. May 2006;15(3):312-321.

6 Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. September 16, 2006;368(9540):1005-1011.

7 Lindroos M, Kupari M, Heikkilä J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. April 1993;21(5):1220-1225.

8 Mack MJ, Brennan JM, Brindis R, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA. November 20, 2013;310(19):2069-2077.

9 Medtronic data on file. 10 lung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart

disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. July 2003;24(13):1231-1243.

11 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. April 1998;113(4):1109-1114.

12 McCarthy CP, Phelan D, Griffin B. When does asymptomatic aortic stenosis warrant surgery? Assessment techniques. Cleve Clin J Med.

13 Brennan JM. Under-treatment of Aortic Stenosis in the United States. Presented at TVT 2019; Chicago, IL.

14 D'Arcy JL, Coffey S, Loudon MA, et al. 2016. Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study†. European Heart Journal 37(47): 3515-22.

15 Everett RJ, et al. Timing of intervention in aortic stenosis: a review of current and future strategies. Heart Epub 2018 doi:10.1136/heartjnl-2017-312304.

16 Active Living Awareness Initiative Survey. Survey included 3400 respondents. Available at: Heart-Valve-Surgery.com.

17 Baumgartner, H., et al. (2017). 2017 ESc/EAcTS Guidelines for the management of valvular heart disease. European Heart Journal, Volume 38, Issue 36, 21 September 2017, Pages 2739–2791, https://doi.org/10.1093/eurheartj/ehx391.

18 Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation. November 1982;66(5):1105-1110.

19 Van Geldorp MW, Heuvelman HJ, Kappetein AP, Busschbach JJ, Takkenberg JJ, Bogers AJ. The effect of aortic valve replacement on quality of life in symptomatic patients with severe aortic stenosis. Neth Heart J. January 2013;21(1):28-35.

20 Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. May 2, 2019;380(18):1706-1715.

21 Forrest JK, Williams MR, Popma JJ, et al. 30-Day outcomes Following Transcatheter Aortic Valve Replacement With the Evolut PRO Valve in commercial Use: A Report from the STS/Acc TVT Registry™. Presented at TcT 2018; San Diego, cA.

22 Data on file (>20 clinical trials with over 20000 patients enrolled). 23 Dahou A, Mahjoub H, Pibarot P. Prosthesis-Patient Mismatch After Aortic Valve

Replacement. Curr Treat Options Cardiovasc Med. November 2016;18(11):67. 24 Dumesnil JG, Pibarot P. Prosthesis-patient mismatch: an update. Curr Cardiol Rep. 2011

Jun;13(3):250-7. 25 Flameng W, Herregods MC, Vercalsteren M, Herijgers P, Bogaerts K, Meuris B. Prosthesis-

patient mismatch predicts structural valve degeneration in bioprosthetic heart valves. Circulation. May 18, 2010;121(19):2123-2129.

26 Pibarot P, Dumesnil JG. Prosthesis-patient mismatch: definition, clinical impact, and prevention. Heart. August 2006;92(8);1022-1029.

27 Van Slooten YJ, van Melle JP, Freling HG, et al. Aortic valve prosthesis-patient mismatch and exercise capacity in adult patients with congenital heart disease. Heart. January 2016;102(2):107-113.

28 Bleiziffer S, Eichinger WB, Hettich I, et al. Impact of patient-prosthesis mismatch on exercise capacity in patients after bioprosthetic aortic valve replacement. Heart. May 2008;94(5):637-641.

29 Herrmann HC, Daneshvar SA, Fonarow GC, et al. Prosthesis-Patient Mismatch in Patients Undergoing Transcatheter Aortic Valve Replacement: From the STS/ACC TVT Registry. J Am Coll Cardiol. December 4, 2018;72(22):2701-2711.

30 Reardon MJ. Primary Results from the Evolut Low Risk Trial. Presented at ACC 2019; New Orleans, LA.

31 Barker CM, Popma JJ, Williams MR, et al. Transcatheter Aortic Valve Replacement with a Repositionable Supra-annular, Self-Expanding, Bioprosthesis in Patients with Severe Aortic Stenosis at High or Extreme Risk for Surgery: 3-Year Results From the EvolutR US Pivotal Trial. Presented at Society for cardiovascular Angiography and Intervention 2019; Las Vegas NV.

32 Capodanno D, Petronio AS, Prendergast B, et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous cardiovascular Interventions (EAPcI) endorsed by the European Society of cardiology (ES c) and the European Association for cardio-Thoracic Surgery (EAcTS). Eur Heart J. December 1, 2017;38(45):3382-3390.

33 Søndergaard L. Long-term follow-up of transcatheter and surgical bioprosthetic aortic valves in patients with severe aortic stenosis and lower surgical risk. presented at PCR Valves e-Course; Movember 24, 2020.

EuropeMedtronic International Trading Sàrl.Route du Molliau 31Case postaleCH-1131 TolochenazTel: +41 (0)21 802 70 00Fax: +41 (0)21 802 79 00

medtronic.eu

See the CoreValve™ Evolut™ R, the CoreValve™ Evolut™ PRO and the Evolut™ PRO+ device manuals for detailed information regarding the instructions for use, the implant procedure, indications, contraindications, warnings, precautions, and potential adverse events. For further information, contact your local Medtronic representative and/or consult the Medtronic website at medtronic.eu.

For applicable products, consult instructions for use on manuals.medtronic.com. Manuals can be viewed using a current version of any major internet browser. For best results, use Adobe Acrobat® Reader with the browser.

The commercial name of the Evolut™ R device is Medtronic CoreValve™ Evolut™ R System, the commercial name of the Evolut™ PRO device is Medtronic CoreValve™ Evolut™ PRO System, and the commercial name of the Evolut™ PRO+ device is Medtronic Evolut™ PRO+ System.

UC202114750EE © Medtronic 2021.All rights reserved.

Actor Portrayal