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 Etiologies
The Challenge of Cryptogenic Stroke
Vessel Rupture (15%) Artery Occlusion (85%)

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

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

Cryptogenic Stroke
Why AF Matters
AF equals 5 fold increase for stroke risk Up to 90% of Paroxysmal Atrial Fibrillation (PAF) episodes may be asymptomatic. Risk of stroke annually is equal for PAF and permanent AF Detection of AF in Cryptogenic Stroke Patients changes treatment
Guidelines state change from antiplatelet to OAC4

1. 2. 3. 4.

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

How AF is Detected in Cryptogenic Stroke Patients The 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
30%

Incremental % AF Detection
Acute Workup After CS Diagnosis
Cotter / Ritter Data

20%

10%
2.7% 0%

4.1%

5.0%

5.7%

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):1546-50 3. 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 Analysis

Newly Detected AF (NDAF) in Patients with Thromboembolic Events
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

1.0

89% of NDAF patients identified beyond 1 day 78% of NDAF patients identified beyond 7 days

0.9

60% of NDAF patients identified beyond 30 days

Freedom from AT/AF

0.8

0.7

0.6

0.5
0 Number 163 at Risk: 3 mo. 127 6 mo. 111 9 mo. 106 12 mo. 67

Time from Device Implant (months)

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.

Occult Atrial Fibrillation in Cryptogenic Stroke

Detection by 7-day ECG vs. ICM
Ritter 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 Stroke

Cotter 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 Report
Etgen 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 ICM
Product Overview

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

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.

Reveal XT ICM Minimally Invasive Outpatient Procedure

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

Cardiac Compass Report

Trended Diagnostics

Daily AF Burden

Ventricular Rate During AF Day/Night HR Patient Activity Heart Rate Variability

Reveal XT ICM 2 Forms of Data Follow-Up

The Medtronic Programmer (in-office) 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 LaterReveal XT ICM Documents AF

Electrophysiology Worksheet

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

Cardiac Compass Report

First InterrogationNo 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 patients AF Burden