CRYPTOGENIC STROKE. Reveal LINQ TM THERAPY AWARENESS PRESENTATION

Transcription

1 CRYPTOGENIC STROKE Reveal LINQ TM Insertable Insertable Cardiac Cardiac Monitoring Monitoring System System THERAPY AWARENESS PRESENTATION

2 AGENDA Epidemiology Diagnosis & Monitoring Strategies Evidence Guidelines Reveal LINQ System Cryptogenic Stroke Care Pathway Patient Case Study

3 EPIDEMIOLOGY

4 STROKE AS A HEALTHCARE ISSUE IN EUROPE 1.6 MILLION STROKES OCCUR EACH YEAR THE LEADING CAUSE OF DISABILITY IN ADULTS STROKE IS THE 2 ND MOST COMMON CAUSE OF DEATH Wilkins E, Wilson L, Wickramasinghe K, et al. European Cardiovascular Disease Statistics 2017 edition. Eur Heart Network 2017:192 4

5 DISABILITY ASSOCIATED WITH STROKE Percent Remaining hemiparesis Unable to walk without assistance Cognitive deficits Depressive symptoms Aphasia Dependent on others Institutionalized Go AS, et al. Circulation. 2013;127:e6-e245. 5

6 RECURRENT STROKE RATE AMONG PATIENTS DISCHARGED WITH A PRIMARY DIAGNOSIS OF STROKE Recurrent Stroke Rate (%) % % month 6 months 1 year 4 years Feng W, et al. Neurology. 2010;74:

7 RISK FOR STROKE IN PATIENTS WITH AF ATRIAL FIBRILLATION IS A COMMON ARRHYTHMIA THAT MAY BE AT THE ORIGIN OF A STROKE 7

8 RISK FOR STROKE IN PATIENTS WITH AF 5-FOLD increase in ischemic stroke risk for AF patients. 1 2X 67% more likely for decrease in AF patient AF-related ischemic stroke risk with oral stroke to be fatal as anticoagulants. 3 non-af stroke. 2 AF DETECTION AND TREATMENT MATTERS 1 Wolf PA, et al. Arch Intern Med. 1987;147: Lin HJ, et al. Stroke. 1996; 27: Stroke Prevention in Atrial Fibrillation Study. Circulation. 1991;84:

9 WHY TALK ABOUT CRYPTOGENIC STROKE? Despite an excessive diagnostic workup, about 30% of the stroke patients are still cryptogenic 1-6 Ischemic Stroke Large Vessel Small Vessel Other Cryptogenic Stroke Cardioembolic Most cryptogenic stroke patients receive anti-platelet for secondary prevention 7 20% 30% Long-term monitoring reveals AF in ~30% of cryptogenic stroke patients 8 This enables treatment change from antiplatelet to oral anticoagulation 30% Cryptogenic Stroke 5% 15% 1 Sacco RL, et al. Ann Neurol. 1989;25: Petty GW, et al. Stroke. 1999;30: Kolominsky-Rabas PL, et al. Stroke. 2001;32: Schulz UG, et al. Stroke. 2003;34: Schneider AT, et al. Stroke. 2004;35: Lee BI, et al. Cerebrovasc Dis. 2001;12: Kernan WN, et al. Stroke. 2014;45: Sanna T, et al. N Engl J Med. 2014;370:

10 DIAGNOSIS & MONITORING STRATEGIES

11 DEFINITIONS OF CRYPTOGENIC STROKE CLASSIFICATION SCHEME TOAST 1 Causative Classification of Stroke (CCS) % 2 Embolic strokes of undetermined source 3 ASCO(D) phenotyping 4 REQUIRED WORK-UP Not specified Brain CT/MR, 12-lead ECG, precordial echocardiogram, extra/intravascular imaging Brain CT/MR, 12-lead ECG, precordial echocardiogram, extra/intravascular imaging, cardiac monitoring for 24 hours Does not include a cryptogenic stroke category 1 Adams HP, et al. Stroke. 1993;24: Causative Classification System for Ischemic Stroke (CCS). Available at: Accessed April 15, Hart RG, et al. Lancet Neurol. 2014;13: Amarenco P, et al. Cerebrovasc Dis. 2013;36:

12 CRYPTOGENIC STROKE IS A DIAGNOSIS OF EXCLUSION Atherosclerotic Small arterial occlusion % Cardioembolic Other causes Cryptogenic Atherosclerotic* Arteroembolic* Aortoembolic Branch occlusive disease Small arterial occlusion Cardioembolic Paroxysmal atrial fibrillation Paradoxical embolism Other causes Cancer-related coagulopathy Cryptogenic Bang OY, et al. Stroke. 2014;45:

13 CONVENTIONAL MONITORING STRATEGIES Bedside Monitoring Holter Monitor Event Recorder During Stroke Unit or Intensive Care Unit stay Event-triggered recording available Optional storage of cardiac rhythm data 24 hours to 7 days of monitoring External loop recorder Saves all cardiac rhythm data Up to 30 days of monitoring Event-triggered loop recorder Saves events only High false-positives rate 1 62% patient compliance 2 1 Kurka N, Bobinger T, Kallmünzer B et al. Reliability and limitations of automated arrhythmia detection in telemetric monitoring after stroke. Stroke 2015; 46: Vasamreddy CR, et al. J Cardiovasc Electrophysiol. 2006;17:

14 REVEAL LINQ WITH TRURHYTHM THE LONG-TERM MONITORING SOLUTION The smallest, most powerful insertable cardiac monitor One-third the size of a AAA battery (1.2 cc) Up to a 3-year longevity for long-term monitoring 1 MR Conditional at 1.5 and 3.0 Tesla Minimally invasive, simplified insertion procedure % of patients very satisfied or satisfied with Reveal LINQ ICM after insertion 3 Proven smart detection algorithms that streamline data with TruRhythm 1 Reference the Reveal LINQ ICM Clinician Manual for usage parameters. 2 Reveal LINQ Usability Study. Medtronic data on file Pürerfellner H, et al. Heart Rhythm. 2015;12:

15 EVIDENCE

16 CRYSTAL-AF STUDY STUDY DESIGN AND END POINTS 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 End Point 30% Cryptogenic Stroke 15% Primary Time to first detection of AF at 6 months of follow-up Secondary Time to first detection of AF at 12 months Recurrent stroke or TIA Change in use of oral anticoagulant drugs Source: Sanna T, et al. N Engl J Med. 2014;370:

17 CRYSTAL-AF STUDY STUDY POPULATION 447 patients were enrolled 6 were excluded 4 did not meet eligibility criteria 2 withdrew consent 441 underwent randomization 221 were assigned to ICM 208 had ICM inserted 13 did not have ICM inserted 220 were assigned to control 220 received standard of care 12 crossed over to control 12 exited the study 3 died 1 was lost to follow-up 5 withdrew 3 were withdrawn by investigator 6 crossed over to ICM 13 exited the study 2 died 1 was lost to follow-up 7 withdrew 3 were withdrawn by investigator 221 were included in intention-to-treat analysis 220 were included in intention-to-treat analysis Source: Sanna T, et al. N Engl J Med. 2014;370:

18 CRYSTAL-AF STUDY PATIENT INCLUSION CRITERIA Age 40 years Diagnosis of stroke or TIA occurring within previous 90 days Stroke was classified as cryptogenic after extensive testing: 12-lead ECG 24 hours of ECG monitoring TEE Screening for thrombophilic states (in patients < 55 years of age) Magnetic resonance angiography, computerized tomography angiography, or catheter angiography of head and neck Ultrasonography of cervical arteries or transcranial Doppler ultrasonography of intracranial arteries allowed in place of MRA or CTA for patients aged 55 years Patients were only categorized as cryptogenic stroke after extensive diagnostic testing. Source: Sanna T, et al. N Engl J Med. 2014;370:

19 CRYSTAL-AF STUDY SELECTED BASELINE PATIENT CHARACTERISTICS Characteristic ICM (n = 221) Control (n = 220) Age (years) 61.6 ± ± Male 64.3% 62.7% 0.77 White 87.8% 86.8% 0.60 Patent foramen ovale 23.5% 20.9% 0.57 Index event 0.87 Stroke 90.5% 91.4% TIA 9.5% 8.6% P Source: Sanna T, et al. N Engl J Med. 2014;370:

20 CRYSTAL-AF STUDY AF DETECTION RATE CONTINUOUS MONITORING WITH REVEAL ICM IS SUPERIOR TO SOC FOR THE DETECTION OF AF IN CRYPTOGENIC STROKE PATIENTS Source: Sanna T, et al. N Engl J Med. 2014;370:

21 CRYSTAL-AF STUDY LEARNINGS 84 DAYS is the median time to AF detection in cryptogenic stroke patients (12 months endpoint) 79% of first AF episodes were asymptomatic at 12 months 88% of patients who had AF would have been missed if only monitored for 30 days * * Based on Kaplan Meier estimates. Source: Sanna T, et al. N Engl J Med. 2014;370:

22 CRYSTAL-AF STUDY COMPARISON OF SHORT-TERM MONITORING AND ICMS 79% of first AF episodes were asymptomatic at 12 months 1 SHORT- AND INTERMEDIATE-TERM MONITORING MAY MISS MANY PATIENTS WITH PAROXYSMAL AF Note: For illustrative purposes only. 1 Sanna T, et al. N Engl J Med. 2014;370:

23 CRYSTAL-AF STUDY CLINICAL IMPACT CLINICAL IMPACT: MORE APPROPRIATE CARE Short-term cardiac monitoring is NOT sufficient for AF detection in cryptogenic stroke Extensive external monitoring only 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, hour Holters, and 1 event recorder used. Reveal ICM detected over 7 times more patients with AF at the 12-month end point Source: Sanna T, et al. N Engl J Med. 2014;370:

24 SUMMARY OF ICM STUDIES IN CRYPTOGENIC STROKE Study Duration of monitoring (months) Definition of AF Time to Diagnosis (days) Ritter 1 10 >30 seconds Etgen 2 12 >6 minutes Cotter minutes SURPRISE 4 19 >2 minutes Rojo-Martinez minutes Ziegler minutes Poli 7 12 > 2 minutes Jorfida > 5 minutes CRYSTAL AF 9 (ICM arm) >30 seconds Israel 10 (ESUS patients) 12 2 minutes MULTIPLE STUDIES HAVE ASSESSED THE ABILITY OF ICMS TO DETECT AF IN PATIENTS WITH CRYPTOGENIC STROKE AF detection rate (%) 1 Ritter et al, Stroke. 2013, 44: ; 2 Etgen et al, Stroke. 44: ; 3 Cotter et al, Neurology. 2013, 80: ; 4 Christensen et al, Eur J Neurol. 2014, 21:884-89; 5 Rojo-Martinez Rev Neurol 2013; 57 (6): ; 6 Ziegler et al. Int J Cardiol, 2017; 244: ; 7 Poli Eur J Neurol Feb; 23(2):375-81; 8 Jorfida J et al, Cardiovasc Med (Hagerstown) Dec;17(12): Sanna T et al, NEJM. 2014;370: ; 10 Isreal C, et al. Thromb Haemost Oct 5;117(10):

25 REAL WORLD VALIDATION OF CRYSTAL AF RESULTS Rogers, AAN, real-world cryptogenic stroke patients monitored by Reveal LINQ Cryptogenic stroke diagnosis: physician s discretion Follow-up: 12 months Diagnostic yield at 12 months: 16.3% (n=147) Median time to detection: 86 days Analysis supports results of CRYSTAL AF Continuous monitoring for periods longer 30 days may be warranted in CS patients 72% of AF patients would be missed if monitoring stopped at 30 days Rogers J et al, American Academy of Neurology,

26 LONG-TERM DETECTION OF ATRIAL FIBRILLATION WITH INSERTABLE CARDIAC MONITORS IN A REAL-WORLD CRYPTOGENIC STROKE POPULATION Ziegler et al., cryptogenic stroke patients in the DiscoveryLink database Follow-up: up to 2 years (579 ± 222 days) AF 2 min was detected in 16.3% at 1 year and in 21.5% at 2 years (vs. 4.6% at 30 days) Median time to AF detection: 112 days (IQR ) In 74% of patients, the longest episode was >1h In most patents with multiple AF episodes, durations increased following initial episode 79% of AF patients would have been missed with 30 days of monitoring Median duration of longest AF episode: 4.0 [ ] hours Ziegler et al. Int J Cardiol, 2017; 244:

27 PREDICTORS OF AF OFFER ONLY POOR PREDICTIVE ABILITY CRYSTAL AF sub-analysis: Thijs, Neurology Parameters tested: Age, sex, race Body Mass Index, Type and severity of index event CHADS 2 score PR-interval Diabetes, hypertension Congestive heart failure Patent foramen ovale Premature atrial contractions Increasing age and a prolonged PR-interval were independently associated with AF, but the predictive ability of these parameters was only moderate Thijs et al. Predictors for Atrial Fibrillation Detection after Cryptogenic Stroke: Results from CRYSTAL AF. Neurology (in press) 27

28 CONTINUOUS MONITORING IS SUPERIOR TO INTERMITTENT CRYSTAL AF sub-analysis: Choe, Am J Cardiol 2015 Simulated intermittent monitoring was compared to continuous rhythm monitoring in 168 ICM patients Sensitivity was low: % Negative predictive value: % 100 Short-term Monitoring 24-hour 48-hour 7-day Holter 21-day event recorder 30-day event recorders Periodic Monitoring Quarterly 24-hour Holters Quarterly 48-hour Holters Quarterly 7-day Holters Monthly 24-hour Holters Sensitivity (%) Negative Predictive Value (%) Intermittent rhythm monitoring would have failed to identify previously undiagnosed AF in the vast majority of CS patients 0 24-Hour 48-Hour 7-Day 21-Day 30-Day 4 Quarterly 24-hr Holters 4 Quarterly 48-hr Holters 4 Quarterly 7-day Holters MONITORING METHOD all p<0.001 vs. Continuous Monitoring 12 Monthly 24-hr Holters Choe et al. A comparison of atrial fibrillation monitoring strategies after cryptogenic stroke (from the CRYSTAL AF trial). Am J Cardiol. 2015;116:

29 DETECTION OF AF IN ESUS PATIENTS Israel C. et al, Thromb Haemost Oct 123 ESUS patients with ICM Mean follow-up for 12 months Average time between stroke and implant: 20 days Interrogation daily using remote monitoring Results: AF detected is 23.6% Average time to detection was 3.6 months AF was found in about 1 out of 4 patients using the ESUS criteria for selection. The patients have been monitored remotely for a mean duration of 12 months. DEFINITION OF ESUS Imaging showing embolic infarction Ultrasound of brain-supplying arteries Routine ECG 72-hour continuous rhythm monitoring on the stroke unit Additional 24-h 72 h Holter ECG Transesophageal echocardiography Transthoracal echocardiography Laboratory testing to disclose thrombophilia, M. Fabry, etc. Isreal C, et al. Thromb Haemost Oct 5;117(10):

30 SUMMARY: DAYS TO DETECTION OF AF IN CLINICAL STUDIES OF ICMS Days from Insertion Cotter (2 min) Etgen (6 min) Ritter (2 min) Rojo-Martinez (2 min) SURPRISE (2 min) CRYSTAL AF (2 min) Real World 7 (2 min) Israel (2 min) 8 N = 51 N = 22 N = 60 N = 101 N = 85 N = 441 N = 1247 N = Cotter PE, et al. Neurology. 2013;80: Etgen T, et al. Stroke. 2013;44: Ritter MA, et al. Stroke. 2013;44: Rojo-Martinez E, et al. Rev Neurol. 2013;57: Christensen LM, et al. Eur J Neurol. 2014;21: Sanna T, et al. N Engl J Med. 2014;370: Ziegler et al. Int J Cardiol, 2017; 244: Isreal C, et al. Thromb Haemost Oct 5;117(10):

31 SUMMARY: AF DETECTION YIELD IN CLINICAL STUDIES OF ICMS AF Detection Yield (%) , Cotter (2 min) Etgen (6 min) Ritter (2 min) Rojo-Martinez (2 min) SURPRISE (2 min) CRYSTAL AF* (2 min) N = 51 N = 22 N = 60 N = 101 N = 85 N = 441 Real-World 7 (2 min) N = 1247 Israel (2 min) N = Cotter PE, et al. Neurology. 2013;80: Etgen T, et al. Stroke. 2013;44: Ritter MA, et al. Stroke. 2013;44: Rojo-Martinez E, et al. Rev Neurol. 2013;57: Christensen LM, et al. Eur J Neurol. 2014;21: Sanna T, et al. N Engl J Med. 2014;370: Ziegler et al. Int J Cardiol, 2017; 244: Isreal C, et al. Thromb Haemost Oct 5;117(10):

32 GUIDELINES

33 2016 ESC AF GUIDELINES Actual ESC guidelines on the diagnosis and management of AF European Stroke Organization endorsed these guidelines Kirchhof P, et al. Eur Heart J Aug 27. pii: ehw

34 2016 ESC AF GUIDELINES ICM RECOMMENDATION FOR CRYPTOGENIC STROKE RECOMMENDATION CLASS LEVEL In stroke patients, additional ECG monitoring by long-term non- invasive ECG monitors or implanted loop recorders should be considered to document silent atrial fibrillation. IIa B Classes of recommendations Class IIa Definition Weight of evidence/opinion is in favour of usefulness/efficacy. Suggested wording to use Should be considered Level of evidence B Data derived from a single randomized clinical trial or large non-randomized studies. Kirchhof P, et al. Eur Heart J Aug 27. pii: ehw

35 REVEAL LINQ SYSTEM

36 REVEAL LINQ SYSTEM ADVANTAGES SIMPLE INSERTION PROCEDURE Best location: 45 degrees to sternum over 4th intercostal space, 2 cm from left edge of sternum 97% of physicians found the insertion tool simple and intuitive. 1 Requires minimal procedure time and clinical resources 1 Reveal LINQ Usability Study. Medtronic data on file

37 TRURHYTHM DETECTION INSIDE ACCURACY EVOLUTION TruRhythm Detection Reveal LINQ Reveal XT Reveal XT With FullView Software Streamlined episode review for clinic efficiency 1,2 PAUSE NEW Pause algorithm with diminishing R-wave analysis NEW simplified insertion and tight pocket for better signal NEW algorithms with Smart filtering Self-learning intelligence AF Industry s first AF detection algorithm AF NEW AF algorithm and improved noise discrimination AF NEW AF algorithm with increased accuracy BRADY PAUSE AF TruRhythm Detection Efficiency. Medtronic data on file TruRhythm Detection Algorithms. Medtronic data on file

38 TRURHYTHM INTELLIGENT DETECTION NEW ALGORITHMS SMART FILTERING NEW second sensing filter analyzes rhythms for possible undersensing in Brady and Pause SELF-LEARNING Exclusive fifth-generation atrial fibrillation algorithm learns and adapts to patient s rhythm over time BRADY & PAUSE AF 38

39 REVEAL LINQ ICM SYSTEM PROVEN ARRYTHMIA DETECTION. INFORMED CLINICAL DECISIONS. 99.7% Reveal LINQ ICM is proven to find AF Highest published AF detection accuracy on the market, at 99.7% As the most clinically-validated ICM, with 50+ detection performance papers, Reveal LINQ ICM is the reliable choice for arrhythmia management 2 1. Sanders P, Pürerfellner H, Pokushalov E, et al. Performance of a New Atrial Fibrillation Detection Algorithm in a Miniaturized ICM: Results from the Reveal LINQ Usability Study. Heart Rhythm. July 2016;13(7): Medtronic Reveal AF Publications. Medtronic data on file

40 TRURHYTHM PROVEN DETECTION CONFIDENCE ACROSS INDICATIONS Cryptogenic stroke Syncope Atrial fibrillation Why Reveal LINQ ICM? 88% percent of AF patients would be missed if monitoring stopped at 30 days* 1 Why Reveal LINQ ICM? 78% of patients with recurrent syncope are diagnosed with an ICM 3 Why Reveal LINQ ICM? Short and intermittent monitoring will likely miss many patients with paroxysmal AF 1 Why TruRhythm Detection? Don t miss an AF episode with high sensitivity and streamlined data review 2 Why TruRhythm Detection? Spend half the time reviewing false detect data, with significant improvement in Brady and Pause detections** 2,4 The Reveal LINQ ICM is guideline-recommended for Cryptogenic Stroke and Syncope 5,6 Why TruRhythm Detection? Manage AF patients over time with more actionable and accurate reports 2 1 Sanna T, et al. N Engl J Med. 2014;370(26): TruRhythm Detection Algorithms. Medtronic data on file Edvardsson N, et al. Europace. 2011;13(2): TruRhythm Detection Efficiency. Medtronic data on file Kirchhof P, et al. Eur Heart J. Published online August 27, Accessed online August 31, Task Force for the Diagnosis and Management of Syncope, et al. Eur Heart J. November 2009;30(21): * Based on Kaplan Meier estimates Episodes detected are 2 minutes ** Compared with the Reveal LINQ ICM without TruRhythm Detection 40

41 CLINICAL RIGOR EVIDENCE SUPERIORITY. REAL-WORLD IMPACT. Most Studied ICM With an evidence portfolio of 500+ published clinical articles and abstracts 1 With an evidence portfolio of 500+ published clinical articles and abstracts 1 Most Clinically Validated ICM Across Cryptogenic Stroke, Syncope, and Atrial Fibrillation patient populations 2-4 Across Cryptogenic Stroke, Syncope, and Atrial Fibrillation patient populations 8-10 Only ICM with Premier Clinical Evidence Published in multiple premier journals, including Heart Rhythm, The New England Journal of Medicine, and JACC 2,3,5 Published in multiple premier journals, including Heart Rhythm, The New England Journal of Medicine and JACC 8,9,11 1 Medtronic Reveal Publications. Medtronic data on file Sanders P, et al. Heart Rhythm. 2016;13: Sanna T, et al. N Engl J Med. 2014;370: Edvardsson N, et al. Europace. 2011;13: Krahn AD, et al. J Am Coll Cardiol. 2003;42:

42 REVEAL LINQ ICM SYSTEM AN ADVANCED MONITORING SOLUTION Reveal LINQ ICM Wireless MyCareLink Cellular with TruRhythm Patient Monitor CareLink Network & Reports SOLUTION ENABLERS Insertion Tools Patient Assistant LINQ Mobile Manager App-based programmer FOCUSON Monitoring Service 42

43 HOW REMOTE MONITORING WORKS THE MEDTRONIC CARELINK SYSTEM Schematic representation of the CareLink system for data transfer between ICM and healthcare professional. 43

44 REVEAL LINQ MOBILE MANAGER SIMPLE, FLEXIBLE, CONNECTED Reveal LINQ Mobile Manager is an innovative app-based programming solution for Reveal LINQ devices: A flexible tablet-based system for both ios and Android operating systems. Communicates wirelessly via Bluetooth technology built into our Medtronic patient connector. The simplicity, flexibility and connectivity continue to receive positive reviews from our customers. NEW REVEAL LINQ MOBILE MANAGER EXPERIENCE With feedback from clinicians worldwide, Medtronic continues to enhance the Reveal LINQ Mobile Manager system with updates to our app that include upgraded security and enhanced data visibility. 44

45 FOCUSON SUPERIOR MONITORING AND TRIAGE SERVICE A service that saves time for healthcare professionals and enables a higher quality of care. THE CONTINUOUS FOCUSON PROCESS The FOCUSON service is built around a highly skilled team that classifies transmitted patient data based on agreed protocol and promptly notifies the physician, allowing efficient and effective patient treatment. TIMELY, ACTIONABLE INSIGHTS FOCUSON notifies hospital Clinical Teams with the insights they need, when they need them, using phone and communication prioritized by color-coding. 2m Multilingual team of cardiologists and ECG technicians with 2 million ECGs of experience since Quality of monitoring 66,000 ECGs per year 1 1 Medtronic and Fysiologic BV data on file 45

46 CRYPTOGENIC STROKE CARE PATHWAY

47 ISCHEMIC STROKE WORK-UP STROKE Lacunar infraction: small vessel disease Standard stroke work-up Embolic appearing stroke with no history of AF: Multiple foci of infarction Cortical watershed distribution Cerebellar History of AF? Standard stroke work-up Antiplatelet agent Standard stroke work-up Anticoagulation MRA or CTA of intracranial vessels Transesophageal Echocardiogram (TEE) Symptomatic carotid stenosis greater than 50% Intracranial stenosis Positive TEE All testing negative? CEA or stent Anticoagulant Monofocal Multifocal Medical management Antiplatelet agents Angiogram Lumbar puncture Vasculitis work-up 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/ TIA 47

48 CRYPTOGENIC STROKE PATHWAY Pathway based on the consensus of the Cryptogenic Stroke Pathway steering committee. February 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. 48

49 CONCLUSIONS Approximately one-third of ischemic strokes are classified as cryptogenic Up to 30% of cryptogenic stroke patients have undiagnosed AF The more you look, the more you find Short- to intermediate-term cardiac rhythm monitoring may not be enough to detect paroxysmal AF in your cryptogenic stroke patients CRYSTAL-AF demonstrates superiority of continuous, long-term monitoring of cryptogenic stroke patients with an ICM 2016 ESC guidelines recommend monitoring with ICMs in cryptogenic stroke patients Reveal LINQ ICM Up to 3 years of continuous cardiac monitoring with the world s smallest ICM Proven AF detection algorithm with industry leading accuracy Safe for use in MRI setting same day at 1.5 and 3.0 Tesla* *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.

50 PATIENT CASE STUDY

51 CRYPTOGENIC STROKE PATIENT IMPACT SCOTT S STORY Reveal LINQ ICM used to discover AF in 22-year-old stroke patient On his way to a soccer game, 22-year-old Scott suddenly began wobbling. His head started throbbing. What he thought was dehydration turned out to be much worse. The college student had suffered a stroke. Surgeons removed a blood clot in his brain, but a looming question remained: What caused the stroke in this seemingly healthy young man? Scott s doctors suspected it was the result of atrial fibrillation (AF). So Scott s doctors turned to the Reveal LINQ ICM, which, within a few months, confirmed he had AF. The diagnosis not only gave Scott s doctors the information they needed to prescribe stroke-preventive blood thinners; it gave Scott the peace of mind to live life fully again. Actual patient photo. This story reflects one person s FPO experience. Not every person will receive the same results. 51

52 CASE STUDY 51-year-old woman Episode of unsteady gait and dizziness (< 1 hour) On admission: BP 140/86 HR 68 BPM No neurologic deficits 20% After urgent MRI, admitted to intensive care unit for further assessment 52

53 CASE STUDY Two areas of infarct were identified in the left cerebellum MRA of head and neck and chest x-ray returned normal results TTE showed normal LV size and function 20% Subsequent TEE confirmed these results, also showed that her atrial size was at the upper limits of normal TEE showed that there was no thrombus and normal velocities in the LAA,a normal aortic arch, and no evidence of a patent foramen ovale 24-hour telemetry monitoring was negative for arrhythmia 53

54 CASE STUDY Patient discharged on clopidogrel 75 mg/day and was followed for an additional 14 days with MCT No arrhythmias identified during this period 54

55 CASE STUDY Five weeks after her initial stroke presentation, she developed a recurrence of unsteadiness and dizziness Patient also developed a right-sided headache with nausea and vomiting Symptoms lasted 2 hours Patient was admitted to the ICU after an urgent brain MRI 55

56 CASE STUDY 56

57 CASE STUDY SUMMARY The patient underwent extensive additional evaluation, including a work-up for hypercoagulability, which was negative She was subsequently implanted with an ICM and discharged on clopidogrel and aspirin After 2 months of monitoring, episodes of paroxysmal AF lasting 15 to 90 minutes were detected Episodes were asymptomatic despite mean ventricular rates > 120 BPM The patient was subsequently prescribed an oral anticoagulant 57

58 BRIEF STATEMENT See the device manual for detailed information regarding the instructions for use, the implant procedure, indications, contraindications, warnings, precautions, and potential adverse events. If using an MRI SureScan device, see the MRI SureScan technical manual before performing an MRI. For further information contact your local Medtronic representative and/or consult the Medtronic website at Consult instructions for use at this website. Manuals can be viewed using a current version of any major Internet browser. For best results, use Adobe Acrobat Reader with the browser. Important Reminder: This information is intended only for users in markets where Medtronic products and therapies are approved or available for use as indicated within the respective product manuals. Content on specific Medtronic products and therapies is not intended for users in markets that do not have authorization for use. Medtronic and the Medtronic logo are trademarks of Medtronic. *Third party brands are trademarks of their respective owners. All other brands are trademarks of a Medtronic company. Europe Medtronic International Trading Sàrl. Route du Molliau 31 Case postale CH-1131 Tolochenaz Tel: +41 (0) Fax: +41 (0) medtronic.eu United Kingdom/Ireland Medtronic Limited Building 9 Croxley Park Hatters Lane Watford Herts WD18 8WW Tel: +44 (0) Fax: +44 (0) UC aEE 2018 Medtronic. All rights reserved. Printed in Europe.