Cryptogenic Stroke and the Role of Atrial Fibrillation

Long-term Monitoring with Reveal® XT Insertable Cardiac Monitor

Overview

• The Connection between Stroke and AF• Clinical Effectiveness of Long-term Monitoring• Overview of Reveal® XT ICM• Case Study

Stroke EtiologiesThe Challenge of Cryptogenic Stroke

Types of Ischemic Stroke

Atherothrombotic (25-30%)Stenotic artery feeding area of infarction

Cardioembolic (20%)A thrombus or other material dislodges from the heart or aortic arch

Other/Uncommon (5-10%)

Cryptogenic (25-40%)Unknown cause

Artery Occlusion

(85%)

Vessel Rupture

(15%)

Adams HP Jr, Classification of Subtype of Acute Ischemic Stroke. Stroke. Jan 1993; 24; 35-41

Cryptogenic StrokeWhy AF Matters

• AF equals 5 fold increase for stroke risk¹• Up to 90% of Paroxysmal Atrial Fibrillation (PAF) episodes

may be asymptomatic.² • Risk of stroke annually is equal for PAF and permanent AF ³• Detection of AF in Cryptogenic Stroke Patients changes

treatment– Guidelines state change from antiplatelet to OAC4

1. Wolf PA, et al. Stroke 1991;22:983-988 ; 2. Isreal et al, J AM Coll Cardiol. 2004;43:47-52; 3. Page, RL, et al Circulation. 1994;89:224-227 Hart RG, et al Coll Cardiol. 2000; 35:183-187 4. Camm et al, European Heart Journal . 2012; 33, 2719-2747

How AF is Detected in Cryptogenic Stroke PatientsThe more you look, the more AF you find

•N = 1491

•Acute stroke or TIA and no history of AF

•ECG monitoring in Hospital

•24-hour Holter recording if normal ECG

•7-day event monitor if normal Holter

0%

10%

20%

30%

2.7%4.1% 5.0% 5.7%

Incremental % AF DetectionIncremental % AF Detection

Acute Workup

After CS Diagnosis

Cot

ter

/ R

itter

Dat

a

1. Jabaudon D. Et al. Usefulness of Ambulatory 7-Day ECG Monitoring for the Detection of Atrial Fibrillation and Flutter After Acute Stroke and Transient Ischemic Attack Stroke 2004;35:1647-1651.2. Cotter, P.E., et al., Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology, 2013 Apr 23;80(17):1546-503. Ritter, M.A., et al., Occult Atrial Fibrillation in Cryptogenic Stroke: Detection by 7-Day Electrocardiogram Versus Implantable Cardiac Monitors. Stroke, 2013 May;44(5):1449-52.

TRENDS Study Subgroup AnalysisNewly Detected AF (“NDAF”) in Patients with Thromboembolic Events

Ziegler P. et al. Incidence of newly detected atrial arrhythmias via implantable devices in patients with a history of thromboembolic events. Stroke. 2010 Feb;41(2):256-60.

• 163 patients with previous ischemic stroke/TIA, no known AF, were continuous monitored via pacemaker or ICD

• NDAF > 5 minute duration were found in 28% patients.

• 73% of patients had newly detected AT/AF on <10% of follow-up days

Time from Device Implant (months)

0 3 mo. 6 mo. 9 mo. 12 mo.

Free

dom

from

AT/

AF

0.5

0.6

0.7

0.8

0.9

1.0

Number at Risk: 163 127 111 106 67

89% of NDAF patients identified beyond 1 day

78% of NDAF patients identified beyond 7 days

60% of NDAF patients identified beyond 30 days

Occult Atrial Fibrillation in Cryptogenic StrokeDetection by 7-day ECG vs. ICMRitter et al., 2013

Methods:•60 patients with cryptogenic stroke implanted•Compared ICM to 7-day Holter monitor•Patient workup included Cerebral imaging, ECG, 72 hour telemetry, 24-hour Holter, TEE

Results: •AF detected in 17% (10 pts)•Average time to detection 64 days post-stroke•Yield of ICM (17%) vs. 7-day ECG (1.7%) significantly higher p=0.0077

Ritter, M.A., et al., Occult Atrial Fibrillation in Cryptogenic Stroke: Detection by 7-Day Electrocardiogram Versus Implantable Cardiac Monitors. Stroke, 2013 May;44(5):1449-52.

Incidence of Atrial Fibrillation detected by Implantable Loop Recorders in Unexplained StrokeCotter et al, 2013

Methods:•51 patients with cryptogenic stroke implanted •Patient workup included vascular & cardiac imaging, at least 24 hours of cardiac rhythm monitoring

Results:•AF was identified in 25.5% (13) patients •Median time to AF detection after implant was 48 days•Median duration of first detected AF episode was 6 minutes•AF was associate with increasing age (p = 0.018), interarterial conduction block (p = 0.02), left atrial volume (p = 0.025) and the occurrence of atrial premature contractions on preceding external monitoring (p = 0.004)•Clinical action (OAC) was taken on all patients where AF was detected

Cotter, P.E., et al., Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology, 2013 Apr 23;80(17):1546-50

Insertable Cardiac Event Recorder in Detection of Atrial Fibrillation After Cryptogenic Stroke: An Audit ReportEtgen et al., 2013

Methods•Patient work-up included MRI, 12-lead ECG, 24-72 hr. bedside telemetry, 24-hr Holter, TEE, computed tomography/MRI angiography•22 patients with cryptogenic stroke and eligible for oral anticoagulation were implanted with Reveal XT•AF defined as episode ≥ 6 minutes

Results•AF detected in 27.3% (6) patients•Average time to detection post-stroke was 161 days

Etgen et al, Insertable Cardiac Event Recorder in Detection of Atrial Fibrillation After Cryptogenic Stroke: An Audit Report. Stroke. 2013;44:2007-2009

SURPRISE Study Updated Results

Methods:– 85 patients with cryptogenic stroke/TIA and no AF on 24-hour telemetry were implanted

with Reveal XT– All patients had a minimum of 6 months of monitoring

Results•14 of 85 (16.5%) of patients diagnosed with AF

– Median time from stroke onset to first recorded event - 98 days– Average AF burden was 2 hours per day monitored– CHADS2Vasc in AF group was 4.14 vs. 3.24 in no AF (p=0.03)

Christensen LM. et al. Paroxystic Atrial Fibrillation (PAF) in Patients with minor ischemic stroke or transient ischemic attack. 2013 EuroStroke

Reveal® XT ICMProduct Overview

1.Reveal XT has been demonstrated to pose no known hazards in a specified MR environment with specified conditions of use. Please see Reveal XT clinician manual for more details.

No wires or leads

3-year battery longevity

Automatic ECG recording of arrhythmias (Atrial Fibrillation, asystole, bradycardia and Ventricular Tachycardia episodes)

In-office or remote data transmissions via Medtronic CareLink® Network

Only ICM approved for 1.5 and 3.0 T MRI scans1

Simple subcutaneous insertion

Quick outpatient procedure

Reveal XT ICMMinimally Invasive Outpatient Procedure

Minimally invasive outpatient procedure with local anesthetic and no leads or fluoroscopyMinimally invasive outpatient procedure with local anesthetic and no leads or fluoroscopy

Cardiac Compass® ReportTrended Diagnostics

Daily AF Burden

Ventricular Rate During AF

Day/Night HR

Patient Activity

Heart Rate Variability

Reveal XT ICM2 Forms of Data Follow-Up

The Medtronic Programmer (in-office)

The Medtronic Programmer (in-office)

The Medtronic CareLink System(remote follow-up)

The Medtronic CareLink System(remote follow-up)

Reveal XT ICM Case Study

• Pertinent Patient History– 85-year old female with recent ischemic stroke of unknown

cause. No history of syncope or dizziness– No Cardiac History and normal LVEF on ECG– Medications: Atenolol, Simvastatin, Aspirin, Plavix

• Previous Workup– 72 hr Holter Monitor = Results normal– ECG = Normal Sinus Rhythm– Reveal XT ICM implanted

Case Study compliments of Joydeep Ghosh, MD, FACC.

11 Days After Implant… No AF Electrophysiology Worksheet

3 Months Later…Reveal XT ICM Documents AF Electrophysiology Worksheet

AT/AF Summary shows: Pt in AF 19.2%, averaging 4.6 hrs/day

Cardiac Compass® Report

First Interrogation-No AF

Case Summary• Reveal XT ICM documented AF that previous workups

could not prove

• Patient put on Coumadin to prevent another stroke

• Reveal XT ICM remains implanted to continuously monitor the patient’s AF Burden