Are You Looking Long Enough?

REVEAL AF IN YOUR CRYPTOGENIC STROKE PATIENTS

Reveal LINQTM

Insertable Cardiac Monitoring System

30%20%

15%

5%

30%Cryptogenic Stroke

ONE-THIRD OF ISCHEMIC STROKES ARE CRYPTOGENIC (UNEXPLAINED)1-6

Each year, at least 200,000 cryptogenic strokes occur in the United States7

Cryptogenic stroke accounts for approximately one-third of ischemic strokes in the majority of modern stroke registries and databases1-6

■ Cryptogenic stroke is as prevalent as large vessel stroke

■ Cryptogenic Stroke

■ Large Vessel

■ Small Vessel

■ Other

■ Cardioembolic

2016 ESC Guidelines for the management of atrial fibrillation11

■ Guidelines developed by the Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)

■ Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC

■ Endorsed by the European Stroke Organisation (ESO)

GuidelinesRecommendation In stroke patients, additional ECG monitoring by long-term noninvasive ECG monitors or implanted loop recorders should be considered to document silent atrial fibrillation.

HOW DO YOU MONITOR FOR AF IN YOUR CRYPTOGENIC STROKE PATIENTS?

increase in ischemic stroke risk for AF patients.8

more likely for AF-related ischemic stroke to be fatal as non-AF stroke.9

decrease in AF patient stroke risk with oral anticoagulants.10

5-FOLD 2X 67%

AF DETECTION AND TREATMENT MATTERS

ClassIIa

LevelB

AF detection and monitoring modality selection matters for cryptogenic stroke patients■ The ability to identify AF in patients with cryptogenic stroke has

profound implications for long-term medical management12

■ Recurrence was more frequent and functional deficits were more likely to be severe among survivors of AF-related ischemic stroke9

■ Guidelines also recommend anticoagulant therapy for stroke prevention in most patients with AF13

ARE YOU MONITORING CRYPTOGENIC STROKE PATIENTS LONG ENOUGH?Short- and intermediate-term cardiac monitoring may miss many patients with paroxysmal AF14

AF episode

Repeated short-term monitoring

Long-term, continuous monitoring (up to 3 years)

84 DAYSis the median time to AF detection in cryptogenic stroke patients14

79%of first AF episodes were asymptomatic at 12 months14

88%of patients who had AF would have been missed if only monitored for 30 days*14

*Based on Kaplan Meier estimates.

Median time to detect AF following cryptogenic stroke:13

30 days 12 months 24 months 36 months

Short-term monitoring (up to 1 week)Intermediate-term monitoring (up to 30 days)

DIAGNOSIS OF CRYPTOGENIC STROKE

Note: Illustration purposes only

84 DAYS

INFORM YOUR CLINICAL DECISIONS WITH THEREVEAL LINQ™ ICM SYSTEM

Up to 3 YEARS of continuous cardiac monitoring

The revolutionary Reveal LINQ Insertable Cardiac Monitoring System transforms your ability to diagnose atrial fibrillation with its proven AF detection algorithm

*Reveal LINQ ICM has been demonstrated to pose no known hazards in a specified MRI environment with specified conditions of use. Please see the Reveal LINQ ICM clinician manual or MRI technical manual for more details.

The Reveal LINQ ICM continuously records heart rhythm data and sends them wirelessly to the MyCareLinkTM Patient Monitor

The MyCareLink Patient Monitor transmits data from the Reveal LINQ ICM to the clinic via a global cellular connection

The clinic receives easy-to-use and clinically actionable Reveal LINQ reports via the CareLinkTM Network

The world’s smallest insertable cardiac monitor

■ The Reveal LINQ ICM is placed just under the skin of the patient’s chest in a simple procedure

■ The ultra-discreet heart monitor is not visible in most patients■ Patients prefer the Reveal LINQ ICM over external wearable monitors15

Simple, minimally invasive insertion procedure

Safe for use in MRI setting same day at 1.5 and 3.0 Tesla*

THE CRYSTAL-AF STUDY DEMONSTRATES THE SUPERIORITY OF ICM FOR AF DETECTION IN PATIENTS WITH CRYPTOGENIC STROKE13

■ Randomized, controlled clinical trial with 441 patients ■ Compared continuous, long-term monitoring with Reveal™ ICM

vs. conventional follow-up ■ Assessment at scheduled and unscheduled visits■ ECG monitoring performed at the discretion of the site investigator

■ ≥ 40 years of age■ Cryptogenic stroke (or clinical TIA) with infarct seen on MRI or CT

within the previous 90 days and no mechanism identified after:

– 12-lead ECG

– 24-hour ECG monitoring (e.g., Holter)

– Transesophageal echocardiography

– CTA or MRA of head and neck to rule out arterial source

– Screening for hypercoagulable states in patients < 55 years old

Primary ■ Time to first detection of AF at 6 months of follow-up

Secondary ■ Time to first detection of AF at 12 months of follow-up■ Recurrent stroke or TIA ■ Actions taken after patient diagnosed with AF

CRYSTAL-AF study results

Visit CRYSTAL-AF.com for complete study information.

Detection of Atrial Fibrillation by 36 months

Months since randomization

Atr

ial F

ibril

latio

n D

etec

ted

(% o

f pat

ient

s)

# at risk220 194 167 114 72 36 7Control221 191 173 102 57 29 8ICM

0 6 12 18 24 30 36

0

10

20

30 Hazard ratio, 8.8 (95% CI, 3.5 - 22.2)P < 0.001 by log-rank test

Control

Reveal ICM

1.4%2%

3%

8.9%

12.4%

30%

more AF detected at 6 months: 8.9% in ICM group vs. 1.4% in control

more AF detected at 12 months: 12.4% in ICM group vs. 2.0% in control

more AF detected at 36 months: 30% in ICM group vs. 3.0% in control

As published in the New England Journal of Medicine14

STUDY DESIGN

PATIENT INCLUSION CRITERIA

END POINTS

The CRYSTAL-AF Study found that continuous monitoring with Reveal ICM is superior to standard medical care for the detection of AF in cryptogenic stroke patients.

Clinical impact: More appropriate careShort-term cardiac monitoring is NOT sufficient for AF detection in cryptogenic stroke■ Extensive external monitoring found few patients with AF – In the control group at 6 months, only 3 patients were found to have AF; yet

there were 88 conventional ECGs, 20 24-hour Holters, and 1 event recorder used

■ Reveal ICM detected over 7 times more patients with AF at the 12-month end point

6.4X 7.3X 8.8X

6.4X

7.3X

8.8X

ISCHEMIC STROKE PATHWAY

Ischemic Stroke/TIA

Embolic appearing stroke with no history of AF: ■ Multiple foci of infarction ■ Cortical watershed distribution ■ Cerebellar

Lacunar infarction: small vessel disease

History of AF

Standard stroke work-up

Standard stroke work-up

Antiplatelet agent

Symptomatic carotid stenosis

greater than 50%

Intracranial stenosis

Monofocal Multifocal

Positive TEE

All testing negative?

■ Medical management■ Antiplatelet agents

■ Angiogram■ Lumbar puncture■ Vasculitis work-up

Standard stroke work-up:■ Carotid dopplers■ Telemetry bed■ Fasting lipid panel

■ Glucose control■ Blood pressure management■ Hypercoagulation labs if age < 50

CEA or stent Anticoagulant

Anticoagulation

Standard stroke work-up

■ MRA or CTA of intracranial vessels ■ Transesophageal Echocardiogram (TEE)

Used with permission from Matthew C. Holtzman, MD. Neurology Michigan P.C.This pathway represents Dr. Holtzman’s clinical practice. Medical judgment should be used to determine if adopting pathway is appropriate.

CRYPTOGENIC STROKE PATHWAY

Patient Diagnosed with Cryptogenic Stroke/TIA

Refer to cardiology to insert Reveal LINQ ICM

Not a candidate

NOCould detection of suspected AF impact patient management?

YES

Inpatient/outpatient insertion

Inpatient Outpatient

Insert Reveal LINQ ICM prior to discharge

If unable to insert prior to discharge, potential external monitor bridge and schedule Reveal LINQ ICM

Insert expeditiously

Bridge with external monitor

Enroll in CareLink

Network & perform remote monitoring

Schedule clinical follow-up with treating physician and ensure long-term adherence to monitoring

AF detected

AF not detected

Insert Reveal LINQ ICM

Pathway based on the consensus of the Cryptogenic Stroke Pathway steering committee. February 2016.

Medtronic Disclosure Statement: This pathway is provided for educational purposes and should not be considered the exclusive source for this type of information. It is the responsibility of the practitioner to exercise independent clinical judgment.

Refer to the brief statement for indications, warnings/precautions, and complications for the Reveal LINQ ICM.

References1 Sacco RL, Ellenberg JH, Mohr JP, et al. Infarcts of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol.

April 1989;25(4):382-390.

2 Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of incidence and risk factors. Stroke. December 1999;30(12):2513-2516.

3 Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. December 1, 2001;32(12):2735-2740.

4 Schulz UG, Rothwell PM. Differences in vascular risk factors between etiological subtypes of ischemic stroke: importance of population-based studies. Stroke. August 2003;34(8):2050-2059.

5 Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. July 2004;35(7):1552-1556.

6 Lee BI, Nam HS, Heo JH, Kim DI, Yonsei Stroke Team. Yonsei Stroke Registry. Analysis of 1,000 patients with acute cerebral infarctions. Cerebrovasc Dis. 2001;12(3):145-151.

7 American Heart Association. Heart Disease and Stroke Statistics, 2015 Update. Available at: http://www.heart.org/HEARTORG/General/Heart-and-Stroke-Association-Statistics_UCM_319064_SubHomePage.jsp. Accessed April 12, 2015.

8 Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham Study. Arch Intern Med. September 1987;147(9):1561-1564.

9 Lin HJ, Kelly-Hayes M, Beiser AS, et al. Stroke Severity in Atrial Fibrillation: The Framingham Study. Stroke. 1996; 27: 1760-1764.

10 Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. August 1991;84(2):527-539.

11 Kirchhof P, Benussi, S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. Published online August 27, 2016. Accessed online August 31, 2016 at: http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw210.

12 Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. July 2014;45(7):2160-2236.

13 January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. December 2, 2014;64(21):e1-76.

14 Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. June 26, 2014;370(26): 2478-2486.

15 Reveal LINQ Usability Study. Data on file. Medtronic, Inc. 2013.

Brief Statement

Indications

Reveal LINQ™ LNQ11 Insertable Cardiac Monitor and Patient AssistantThe Reveal LINQ Insertable Cardiac Monitor is an implantable patient-activated and automatically-activated monitoring system that records subcutaneous ECG and is indicated in the following cases:■ Patients with clinical syndromes or situations at increased risk of cardiac arrhythmias■ Patients who experience transient symptoms such as dizziness, palpitation, syncope, and chest pain, that may suggest a

cardiac arrhythmia

This device has not specifically been tested for pediatric use.

Patient AssistantThe Patient Assistant is intended for unsupervised patient use away from a hospital or clinic. The Patient Assistant activates the data management feature in the Reveal Insertable Cardiac Monitor to initiate recording of cardiac event data in the implanted device memory.

ContraindicationsThere are no known contraindications for the implant of the Reveal LINQ Insertable Cardiac Monitor. However, the patient’s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated.

Warnings/PrecautionsReveal LINQ LNQ11 Insertable Cardiac MonitorPatients with the Reveal LINQ Insertable Cardiac Monitor should avoid sources of diathermy, high sources of radiation, electrosurgical cautery, external defibrillation, lithotripsy, therapeutic ultrasound, and radiofrequency ablation to avoid electrical reset of the device, and/or inappropriate sensing as described in the Medical procedure and EMI precautions manual. MRI scans should be performed only in a specified MR environment under specified conditions as described in the Reveal LINQ MRI Technical Manual.

Patient AssistantOperation of the Patient Assistant near sources of electromagnetic interference, such as cellular phones, computer monitors, etc., may adversely affect the performance of this device.

Potential ComplicationsPotential complications include, but are not limited to, device rejection phenomena (including local tissue reaction), device migration, infection, and erosion through the skin.

Medtronic MyCareLink™ Patient Monitor, Medtronic CareLink™ Network and CareLink™ Mobile Application

Intended Use The Medtronic MyCareLink Patient Monitor and CareLink Network are indicated for use in the transfer of patient data from some Medtronic implantable cardiac devices based on physician instructions and as described in the product manual. The CareLink Mobile Application is intended to provide current CareLink Network customers access to CareLink Network data via a mobile device for their convenience. The CareLink Mobile Application is not replacing the full workstation, but can be used to review patient data when a physician does not have access to a workstation. These products are not a substitute for appropriate medical attention in the event of an emergency and should only be used as directed by a physician. CareLink Network availability and mobile device accessibility may be unavailable at times due to maintenance or updates, or due to coverage being unavailable in your area. Mobile device access to the Internet is required and subject to coverage availability. Standard text message rates apply.

Contraindications There are no known contraindications.

Warnings and Precautions The MyCareLink Patient Monitor must only be used for interrogating compatible Medtronic implantable devices.

See the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential complications/adverse events. For further information, please call Medtronic at 1-800-328-2518 and/or consult the Medtronic website at www.medtronic.com.

Caution: Federal law (USA) restricts these devices to sale by or on the order of a physician.

Visit CRYSTAL-AF.com for complete study information.

The CRYSTAL-AF Study found that continuous monitoring with Reveal ICM is superior to standard medical care for the detection of AF in cryptogenic stroke patients.

AF-Detection Rate at 3 Years13

30%

2016 ESC AF Guidelines recommend cardiac monitoring with Reveal LINQ ICM for cryptogenic stroke patients.*11

*Endorsed by the European Stroke Organisation

ARE YOU LOOKING LONG ENOUGH?is the median time

to AF detection in cryptogenic stroke patients13

84 Days

INFORM YOURCLINICAL DECISIONS

Reveal LINQTM

Insertable Cardiac Monitoring System

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