Proven Performance, Simply Delivered

Melody®

TRANSCATHETER PULMONARY VALVE THERAPY

Committed to Patients

With Melody® TPV Therapy, children and adults with dysfunctional pulmonary valve conduits have a proven treatment option designed to restore pulmonary valve function and delay the need for surgical intervention. Thousands of patients from around the world have benefited from this therapy.

Transcatheter pulmonary valve replacement with the Melody valve has proven to be a safe and effective treatment for patients with post-operative right ventricular outflow tract (RVOT) conduit dysfunction. The Melody TPV has been proven to:

• Relieve conduit obstruction

• Restore valve function

• Delay the patient’s next surgical conduit replacement

A Less Invasive Approach to Restore Valve Function

Transcatheter Valve DeliveryThe Ensemble delivery system deploys the Melody valve, with fluoroscopic guidance, through the body’s cardiovascular system:

• Simple hand crimping and loading of the valve

• Integrated sheath eliminates the need for an additional sheath and protects the valve during delivery

• Balloon-in-balloon (BIB) technology for controlled deployment of the valve

Pulmonary Valve DesignThe Melody valve is specifically designed to treat RVOT valve dysfunction. Comprised of a bovine jugular vein (BJV) valve sutured within a platinum iridium frame:

• Natural venous valve leaflets open and close under minimal pressure for optimal hemodynamics

• Deep coaptation of leaflets provides valve competency across a range of conduit sizes and geometries

• Radiopaque stent for visualization ease

1. McElhinney DB, Cheatham JP, Jones TK, et al. Stent fracture, valve dysfunction, and right ventricular outflow tract reintervention after transcatheter pulmonary valve implantation: patient-related and procedural risk factors in the US Melody Valve Trial. Circ Cardiovasc Interv. 2011 Dec 1;4(6):602-14. Epub 2011 Nov 9.

2. McElhinney DB, Hellenbrand WE, Zahn EM, et al. Short- and medium-term outcomes after transcatheter pulmonary valve placement in the expanded multicenter US melody valve trial. Circulation. 2010;122:507-16.3. Armstrong AK, Balzer DT, Cabalka AK, et al. One-year follow-up of the Melody transcatheter pulmonary valve multicenter post-approval study. JACC Cardiovasc Interv. 2014 Nov;7(11):1254-62.4. Lurz P, Coats L, Khambadkone S, et al. Percutaneous pulmonary valve implantation: impact of evolving technology and learning curve on clinical outcome. Circulation. 2008 Apr 15;117(15):1964-72. Epub 2008 Apr 7.5. Eicken A, Ewert P, Hager A, et al. Percutaneous pulmonary valve implantation: two-centre experience with more than 100 patients. Eur Heart J. 2011 May;32(10):1260-5. Epub 2011 Jan 27.6. Butera G, Milanesi O, Spadoni I, et al. Melody transcatheter pulmonary valve implantation. Results from the registry of the Italian Society of Pediatric Cardiology (SICP). Catheter Cardiovasc Interv. 2012 Jun 21. doi: 10.1002/

ccd.24518. [Epub ahead of print].7. Vezmar M, Chaturvedi R, Lee KJ, et al. Percutaneous pulmonary valve implantation in the young 2-year follow-up. JACC Cardiovasc Interv. 2010 Apr;3(4):439-48.8. Fraisse A, Aldebert P, Malekzadeh-Milani S, et al. Melody transcatheter pulmonary valve implantation: Results from a French registry. Arch Cardiovasc Dis. 2014 Nov;107(11):607-14. doi: 10.1016/j.acvd.2014.10.001. Epub 2014 Nov 6.

Substantial Clinical Evidence

Study Number of Centers

Number of Patients First Implant Last Implant Reported Data

US IDE Study1,2 5 150 2007 2010 3 years

US PAS3 10 100 2010 2012 1 year

EU/CA PMSS1 7 63 2007 2009 5 years

UK Experience4 1 155 2000 2007 5.8 years

German Study5 2 102 2006 2010 1 year

Italian Registry6 6 63 2007 2010 1 year

Canadian Experience7 1 28 2005 2008 3 years

French Registry8 5 64 2008 2010 5 Years

Melody TPV Clinical Experience

Since 2007, accumulated data on the Melody TPV and Ensemble Delivery System consistently demonstrates excellent clinical results. The data presented on the following pages are from these three studies:

US IDE StudyProspective, non-randomized investigational study conducted at 5 centers. 150 subjects implanted between January 2007 and January 2010; patients will be followed for 10 years. Data presented is interim results current through March 1, 2014 (mean length of follow-up 4.4 ± 1.3 years).

US Post Approval Study (PAS)Prospective, non-randomized study conducted at 10 centers. 100 subjects implanted between July 2010 and July 2012; patients will be followed for 5 years. Data presented is interim results through March 1, 2014 (mean length of follow-up 2.1 ± 0.8 years).

European and Canadian Post-Market Surveillance Study (PMSS)Prospective, non-randomized study conducted at 7 centers in Europe and Canada. 63 subjects implanted between October 2007 and April 2009; patients will be followed for 5 years. Data presented is interim results through March 1, 2014 (mean length of follow-up 4.2 ± 1.1 years).

IDE StudyPASPMSS

Number at risk:

0%0

149 145 144 128 108 6399 91 62 1862 60 58 56 53 13

1 2 3 4 5

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Free

dom

Fro

m C

ondu

it R

eope

rati

on

Years Post-Implant

98.4%

99.3%

97.9% 91.7%

91.7%

Low rates of surgical conduit reoperation out to 5 years.

Delays Patient’s Next Surgical Intervention

Proven Performance

IDE StudyPASPMSS

Number at risk:

0%0

149 142 133 113 90 5099 91 63 1762 55 50 48 46 11

1 2 3 4 5

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Free

dom

from

Re-

Inte

rven

tion

Years Post Implant

100%

97.3%91.8%

79.5%80.9%

Freedom from catheter-based re-intervention on the TPV was greater than 80% out to 5 years.

Freedom from Catheter Re-intervention

Following Melody TPV implant the mean RVOT gradients decreased and remained consistent throughout follow-up in all 3 studies.

Low RVOT Gradients

Mean RVOT Gradient By Time Interval Baseline 1 Year 3 Year 5 Year

IDE Study (N=149) 32.1 ± 13.9 18.7 ± 9.1 17.5 ± 7.8 17.1 ± 7.5

Post-Approval Study (N=99) 33.4 ± 14.1 15.1 ± 7.1 19.5 ± 15.4 --

Post-Market Surveillance Study (N=62) 37.7 ± 12.1 17.9 ± 9.2 17.3 ± 8.4 16.4 ± 8.6

Excellent Valve Performance

15

20

25

30

35

40

0

5

10

Baseline 1 Year 2 Year 3 Year 4 Year 5 Year

PMSS

IDE StudyPAS

Mea

n RV

OT

Gra

dien

t (m

m H

g)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

IDE

PAS

PMSS

PMSSID

E

PAS

PMSSID

E

PAS

IDE

PMSS

5 Years3 Years1 YearBaseline

None

Trace

Mild

Moderate

Severe

Pulm

onar

y Re

gurg

itat

ion

Rate

s

The majority of subjects in all 3 studies had a moderate or severe pulmonary regurgitation at baseline. Throughout follow-up, the majority of subjects had no more than trace pulmonary regurgitation.

IDE Study (N=149) PAS (N=99) PMSS (N=62)

Minimal Regurgitation

Excellent Valve Performance

Study Subjects with Procedure Success

IDE Study (N=149) 94.7%

Post-Approval Study (N=99) 92.1%

Post-Market Surveillance Study (N=62) 85.7%*

Consistently high rates of successful valve implantation across the three studies including strong hemodynamics and low incidence of procedural adverse events.Procedural success is a composite outcome defined as:• Melody TPV was successfully delivered to the intended location• RV-PA peak-to-peak gradient (measured in the catheterization lab) less than 35mmHg post implant• Less than mild pulmonary regurgitation• Free of explant at 24 hours post implant

* 3 subjects were not assessed for one or more of the composite variables and were considered a procedural failure.

High Rates of Acute Procedural Success

Procedural Success and Strong Safety Profile

IDE Study PMSS PAS

EventFreedom from event

at 5 years (SE) (N=149)Freedom from event at 4 years (SE) (N=62)

Freedom from event at 2 years (SE) (N=99)

Stent Fracture: Major 84.3% (4.5%) 91.5% (3.8%) 97.6% (1.9%)

Valve Dysfunction: Stenosis 79.9% (4.9%) 86.1% (4.7%) 96.3% (2.3%)

Valve Dysfunction: Regurgitation 99.2% (1.1%) 98.3% (1.8%) 96.7% (2.3%)

Prosthetic Valve Endocarditis 96.1% (2.4%) 94.9% (3.0%) 92.9% (3.2%)

Embolization of the TPV 100.0% (-) 100% (-) 100.0% (-)

The safety profile of the Melody valve remains out to 5 years as evidenced by low rates of serious device-related adverse events across all categories.

Low Rates of Device-Related Adverse Events

Procedural Success and Strong Safety Profile

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Class I

IDE

PAS

PMSS

PMSSID

E

PAS

PMSSID

E

PAS

IDE

PMSS

5 Years3 Years1 YearBaseline

Class II

Class III

Class IV

NYH

A F

unct

iona

l Cla

ss b

y Ti

me

and

Inte

rval

At baseline, the majority of subjects in all 3 studies were in NYHA class II/III. Following Melody TPV implant, the majority of subjects were in NYHA class I, which remained consistent during follow-up.

Improves Functional Status

Quality of Life Improvements

IDE Study (N=149) PAS (N=99) PMSS (N=62)

For more information, visit www.Melody-TPV.com

Proven Performance, Simply Delivered

EQ-5D Health State (0-100)

Baseline (N=43) 6 Months (N=40) 1 Year (N=39) 4 Years (N=36)

72.3 ± 20.4 83.1 ± 12.2 85.5 ± 12.4 86.7 ± 12.5

In the PMSS, Quality of Life (QoL) Assessments utilizing the EQ-5D were obtained at baseline and annually throughout follow-up. The EQ-5D Health State demonstrated early improvements that were sustained through follow-up in most categories, including Difficulties with Mobility, Problems with Usual Activities, Pain or Discomfort, and Anxiety or Depression.

Improves Quality of Life

The EQ-5D is a standardized instrument for use as a measure of health outcome applicable to a wide range of health conditions and treatments. It provides a simple descriptive profile and a single index value for health status. A higher Health State score represents an improvement in QoL.

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melody-tpv.com // medtronic.comLifeLine CardioVascular Technical Support Tel: (877) 526-7890 Tel: (763) 526-7890 Fax: (763) 526-7888 E-mail: rs.cstechsupport@medtronic.com

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UC201501804 EN © 2015 Medtronic. All Rights Reserved. 01/2015

Melody® Transcatheter Pulmonary Valve, Ensemble® Transcatheter Valve Delivery SystemImportant Labeling Information for United States.Indications: The Melody TPV is indicated for use as an adjunct to surgery in the management of pediatric and adult patients with the following clinical conditions:• Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter when

originally implanted AND• Dysfunctional RVOT conduits with a clinical indication for intervention, AND:

-regurgitation: ≥ moderate regurgitation, AND/OR -stenosis: mean RVOT gradient ≥ 35 mm Hg

Contraindications: None known.Warnings/Precautions/Side Effects:• DO NOT implant in the aortic or mitral position. Preclinical bench testing of the Melody valve

suggests that valve function and durability will be extremely limited when used in these locations. • DO NOT use if patient’s anatomy precludes introduction of the valve, if the venous anatomy cannot

accommodate a 22-Fr size introducer, or if there is significant obstruction of the central veins.• DO NOT use if there are clinical or biological signs of infection including active endocarditis. Standard

medical and surgical care should be strongly considered in these circumstances. • Assessment of the coronary artery anatomy for the risk of coronary artery compression should be performed

in all patients prior to deployment of the TPV.• To minimize the risk of conduit rupture, do not use a balloon with a diameter greater than 110% of the

nominal diameter (original implant size) of the conduit for pre-dilation of the intended site of deployment, or for deployment of the TPV.

• The potential for stent fracture should be considered in all patients who undergo TPV placement. Radiographic assessment of the stent with chest radiography or fluoroscopy should be included in the routine postoperative evaluation of patients who receive a TPV.

• If a stent fracture is detected, continued monitoring of the stent should be performed in conjunction with clinically appropriate hemodynamic assessment. In patients with stent fracture and significant associated RVOT obstruction or regurgitation, reintervention should be considered in accordance with usual clinical practice.

Potential procedural complications that may result from implantation of the Melody device include the following: rupture of the RVOT conduit, compression of a coronary artery, perforation of a major blood vessel, embolization or migration of the device, perforation of a heart chamber, arrhythmias, allergic reaction to contrast media, cerebrovascular events (TIA, CVA), infection/sepsis, fever, hematoma, radiation-induced erythema, blistering, or peeling of skin, pain, swelling, or bruising at the catheterization site.Potential device-related adverse events that may occur following device implantation include the following: stent fracture,* stent fracture resulting in recurrent obstruction, endocarditis, embolization or migration of the device, valvular dysfunction (stenosis or regurgitation), paravalvular leak, valvular thrombosis, pulmonary thromboembolism, hemolysis.* The term “stent fracture” refers to the fracturing of the Melody TPV. However, in subjects with multiple stents

in the RVOT it is difficult to definitively attribute stent fractures to the Melody frame versus another stent.For additional information, please refer to the Instructions For Use provided with the product.CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician.

Important Labeling Information for Geographies Outside of the United StatesIndications: The Melody® Transcatheter Pulmonary Valve is indicated for use in patients with the following clinical conditions:• Patients with regurgitant prosthetic Right Ventricular Outflow Tract (RVOT) conduits with a clinical

indication for invasive or surgical intervention, OR • Patients with stenotic prosthetic RVOT conduits where the risk of worsening regurgitation is a relative

contraindication to balloon dilatation or stenting. • Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter

when originally implanted. The intended lifetime for the Melody® device is 2 years.Contraindications: • Venous anatomy unable to accommodate a 22 Fr size introducer sheath; Implantation in left heart; • Unfavorable right ventricular outflow tract for good stent anchorage; • Severe right ventricular outflow obstruction, which cannot be dilated by balloon; • Obstruction of the central veins; • Clinical or biological signs of infection; • Active endocarditis; • Known allergy to aspirin or heparin; • Pregnancy. Potential Complications / Adverse Events: Potential procedural complications that may result from implantation of the Melody device include the following: rupture of the RVOT conduit, compression of a coronary artery, perforation of a major blood vessel, embolization or migration of the device, perforation of a heart chamber, arrhythmias, allergic reaction to contrast media, cerebrovascular events (TIA, CVA), infection/sepsis, fever, hematoma, radiation-induced erythema, pain at the catheterization site.Potential device-related adverse events that may occur following device implantation include the following: stent fracture resulting in recurrent obstruction, endocarditis, embolization or migration of the device, valvular dysfunction (stenosis or regurgitation), paravalvular leak, valvular thrombosis, pulmonary thromboembolism, hemolysis.For additional information, please refer to the Instructions For Use provided with the product.The Melody® Transcatheter Pulmonary Valve and Ensemble® Transcatheter Delivery System has received CE Mark approval and is available for distribution in Europe. Additionally, a Medical Device Licence has been granted and the system is available for distribution in Canada.

Melody and Ensemble are registered trademarks of Medtronic.