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NOR-FIB The Nordic Atrial Fibrillation and Stroke Study

NOR-FIB protocol V 1.2. REK 2013/2371 1

The Nordic Atrial Fibrillation and Stroke Study (NOR-FIB)

Atrial Fibrillation in Cryptogenic Stroke and TIA

STUDY PROTOCOL by

Anne Hege Aamodt, MD, PhD, FESO2

David Russell MD, PhD, FESO, FRCP, Prof1,2 Dan Atar, MD PhD, FESC, Prof1,3

1Institute of Clinical Medicine, University of Oslo 2Department of Neurology, Oslo University Hospital3Department of Cardiology, Oslo University Hospital

ClinicalTrials.gov Identifier: NCT02937077 REK 2013/2371



PROTOCOL SYNOPSIS Sponsor: Oslo University Hospital Protocol number: REK2013/2371

ClinicalTrials.gov Identifier: NCT02937077 Title: The Nordic Atrial Fibrillation and Stroke Study (NOR-FIB Study) Study design: International multi-center prospective observational study of the occurrence of AF in cryptogenic stroke / TIA patients with ICMs for 12 months. Objective: To assess the incidence of atrial fibrillation detection using ICM (Reveal LINQ®) in patients with cryptogenic stroke or TIA. To identify biomarkers that can be used as predictors of incident atrial fibrillation. Number of subjects: 500 Number of centers: Up to 25 Duration of study participation: Enrollment: approximately 18 months Follow-up period: 12 months ± 20 days Total study duration: 30 months Primary endpoint: AF detection rate within 12 months Secondary endpoints:

1. AF detection rate within 6 months2. Levels of NT-proBNP and BNP3. Levels of Troponin-T and Troponin-I4. Levels of cardiovascular biomarkers5. CHA2DS2-VASc score prior to stroke or TIA6. Incidence of recurrent stroke or TIA within 12 months.7. Use and type of oral anticoagulation - percentage of patients who are using OAC

drugs at the 12-month follow-up visit.8. Use of antiarrhythmic drugs - percentage of patients who are using antiarrhythmic

drugs at the 12-month follow-up visit.9. Health Outcome as Evaluated by an EQ-5D Questionnaire - EQ-5D quality of life

score, which is a continuous measure of quality of life.

Inclusion criteria: 1. Cryptogenic ischemic stroke or TIA patients ≤ 10 days from symptom start.2. A stroke/TIA is considered to be cryptogenic if no cause can be determined despite an

extensive workup according to the standard protocol of the participating center. Beforeinclusion to the study, the following tests are required to establish the diagnosis ofcryptogenic stroke or TIA†:

a. Brain MRI or CT†.b. 12-lead ECG for AF detection.c. 24-h ECG monitoring for AF detection and premature atrial complex analysis

(e.g. Holter or telemetry).d. TTE (transthoracic echocardiography)e. TEE (transesophageal echocardiography) in patients aged £ 65 yearsf. Colour Duplex ultrasound examination of the pre-cerebral arteries.g. CTA or MRA of head and neck to rule out other causes of stroke.h. Screening for thrombophilia < 50 years of age.

3. Age > 18 years at onset of TIA/stroke.4. A participation consent form signed by the patient or a legally authorized representative.†TIA cases with acute non-lacunar infarct on Diffusion Weighted Imaging are included as



TIA events.

Exclusion criteria: 1. Known etiology of TIA or stroke.2. TIA without documented cerebral ischemia on Diffusion Weighted Imaging.3. Untreated hyperthyroidism.4. Myocardial infarction less than 1 month prior to the stroke or TIA.5. Coronary bypass grafting less than 1 month prior to the stroke or TIA.6. Valvular heart disease requiring immediate surgical intervention.7. History of atrial fibrillation or atrial flutter.8. Patent Foramen Ovale (PFO) or PFO where there is or was an indication to start oral

anticoagulation9. Permanent indication for OAC treatment at enrollment.10. Permanent contra-indication for OAC.11. Life expectancy less than 1 year.12. Pregnancy now or < 3 months.13. An indication for an Implantable Pulse Generator (IPG), Implantable Cardioverter-

Defibrillator (ICD), Cardiac Resynchronization Therapy (CRT) or an implantablehemodynamic monitoring system.

14. Patients otherwise not available for follow-up (e.g. non-resident) or patients withconcurrent disease which may affect clinical outcome (e.g. multiple sclerosis, cancer)

Schedule of assessments Assessment Methods Screening Inclusion 180 days

follow-up Telephone

365 days follow-up

Range 0 0 ±20 days ±20 days NIHSS X X ECG X X X Pre-stroke modified Rankin Scale X

Cerebral MR/CT X Colour Duplex of the precerebral arteries X

24 h Holter X Echocardiography TTE/TEE X Blood labs X X Modified Rankin Scale (mRS) X X Pre-stroke mRS X Pre-stroke Barthel Index X Barthel Index X EuroQol 5D-5L X X Concomitant Medication X X X X Recurrent stroke/TIA X X X Major cardiovascular events X X X Adverse Events X X X X



Table of contents

1. BACKGROUND AND STATUS OF KNOWLEDGE……………………. 5 1.1. Impact on patient care and stroke management………………………… 6

2. HYPOTHESIS AND AIMS………………………………………………… 6

3. FEASIBILITY………………………………………………………………. 63.1. Study design, methods and analyses…………………………………….. 6 3.2. Roles, organization and cooperation ……………………………………. 10 3.3. Plan for milestones, dissemination and publishing……………………… 12 3.4. Implementation plan…………………………………………………………………….. 12 3.5. Funding………………………………………………………………….. 12

4. USER INTERACTION…………………………………………………….. 12

5. ETHICAL PERSPECTIVES………………………………………………. 12

6. REFERENCES……………………………………………………………… 13

7. APPENDIX 1 – INFORMATION AND CONSENT FORM…………...... 15

8. APPENDIX 2 – SOP BLOOD SAMPLES………………………………… 19

9. APPENDIX 3 – ECHOCARDIOGRAPHY SOP…………………………. 20

APPENDIX 4 – REVEAL LINQ AND CARELINK…………………….. 21 4 – REVEAL LINQ AND CARELINK…………………….. 21 10.



1. Background and status of knowledge

Stroke is one of the leading causes of death and disability worldwide resulting in high health-related and economic consequences.1 2 1/4 of strokes are recurrent strokes. Up to 40% of the ischemic strokes and TIAs remain without a definitive etiology despite a modern extensive diagnostic work-up.3, 4, 5 6These are defined as cryptogenic strokes. The risk of stroke recurrence in these patients is considerable and it is therefore very important to determine their etiology so that secondary prevention may be optimal.5 7

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the population, affecting 1-2% of the general population.8 No consensus has been reached about how atrial fibrillation should be investigated in patients with stroke and TIA, and its prevalence after a cryptogenic stroke remains uncertain.9 AF may be responsible for up to 1 of 3 cryptogenic strokes.10, 11 Paroxysmal AF is more common than permanent AF in acute stroke and TIA patients12, but carries the same stroke risk as permanent AF.13 However, the recognition of paroxysmal AF is often missed as most paroxysmal AF patients are asymptomatic and ECG examinations are often carried out intermittently.

Advanced diagnostic techniques, including long-term rhythm monitoring to detect paroxysmal AF may be useful in reducing the proportion of patients diagnosed with cryptogenic strokes.7, 9 The yield has varied greatly in different studies depending on the interval of monitoring from stroke/TIA onset, duration of monitoring, as well as the choice of monitoring device.9

Continuous ECG recordings can be performed using insertable cardiac monitor (ICM) implantable electronic devices or by external devices. One previous study with Reveal XT® showed that the number of ICMs required to detect a first episode of AF was 14 for 6 months of monitoring, 10 for 12 months, and 4 for 36 months.14 However, there were long time intervals from the onset of stroke or TIA to randomization. The likelihood of revealing paroxysmal AF is increased when continuous cardiac monitoring is started early after the onset of symptoms.15 Recently, another ICM, Reveal LINQ® has been developed which weighs less and is considerably less invasive than any previous loop recorder. It requires a short insertion procedure time and clinical resources.16, 17

Cardiovascular biomarkers can be used to predict the probable cause of cryptogenic stroke.18 19 NT-proBNP, a peptide cleaved from pro-BNP to release brain natriuretic peptide, has been shown to be increased in paroxysmal AF patients20, 21 as well as cryptogenic stroke patients with confirmed paroxysmal AF.22 Similarly troponins, another established cardiac biomarkers, are increased in cryptogenic stroke patients with new onset AF.23 Numerous other cardiovascular biomarkers have been studied in relation to thrombus formation and ischemic events in AF.24, 25 26, 27 28 So far the results has been conflicting and further studies are required to address the clinical implications of cardiovascular biomarkers in the prediction of AF-related thromboembolism.

More studies are needed to establish the benefits of AF detection with newer monitoring devices and to identify factors which may help to select patients where prolonged rhythm monitoring would be most successful. New studies are also needed to assess the optimal duration of rhythm monitoring, the best definition of short-term AF where active treatment is required and to evaluate whether intervention results in improved secondary prevention.



1.1. Impact on patient care and stroke management This study will increase knowledge regarding cryptogenic stroke and TIA and hopefully improve the etiological investigations in these patients so that the cause of stroke can be identified in a larger proportion of patients. The identification of AF in cryptogenic stroke and TIA patients is very important as this information is necessary in order to decide whether the patient should be treated with antiplatelet drugs or anticoagulation. Secondary stroke prevention will therefore be considerably improved if a larger proportion of cryptogenic stroke and TIA patients with paroxysmal AF are diagnosed with paroxysmal AF. NOR-FIB is the first Nordic multi-center study in the NORSTROKE and ECRI cooperation and will facilitate further neurovascular research in Norway.

2. Hypothesis and aimsHypothesis

1. Long-term cardiac rhythm monitoring is effective in detecting paroxysmal atrialfibrillation in cryptogenic stroke and TIA patients.

2. Cardiovascular biomarkers can be used to detect cryptogenic stroke patients with anincreased risk of paroxysmal atrial fibrillation.

The aims of the NOR-FIB Study Primary objective:

1. To assess the incidence of atrial fibrillation detection using ICM (Reveal LINQ®) inpatients with cryptogenic stroke or TIA.

2. To identify biomarkers that can be used as predictors of incident atrial fibrillation.

Secondary objectives: 1. To assess the risk of stroke in patients with short-duration episodes with atrial

fibrillation (AF).2. To evaluate whether oral anticoagulation in cryptogenic stroke or TIA patients where

AF is detected results in improved clinical outcome.3. To assess the usefulness of cardiovascular biomarkers to rule out cardioembolic stroke

in cryptogenic stroke and TIA patients.

3. Feasibility3.1. Study design, methods and analyses:This study is a prospective multi-center observational real-life study that will collect datafrom patients admitted with cryptogenic stroke or cryptogenic TIA in stroke units in theNordic countries. Large stroke centers are participating and patients ≥ 18 years of age will beincluded. Periods of atrial fibrillation ≥ 2 minutes will be assessed for the risk ofthromboembolism.29



Figure 1.

The patients will be screened during their admission for the cause of their acute ischemic stroke or TIA. When the investigations are completed and the diagnosis of cryptogenic ischemic stroke/TIA is made, they will be included in the study after the consent form is signed. The ECG rhythm recording should be started as soon as possible and no later than 10 days after the onset of stroke or TIA symptoms. The local coordinator will insert the Reveal LINQ® according to the description and training provided by Medtronic. Continuous ECG monitoring will then be carried out for 12 months. If AF is detected, patients will be contacted and anticoagulation will be started unless there are strong contraindications. The study flow from screening to follow-up is shown in figure 1.

Primary endpoint: AF detection rate within 12 months

Secondary endpoints: AF detection rate within 6 months Levels of NT-proBNP and BNP Levels of Troponin-T and Troponin-I Levels of cardiovascular biomarkers CHA2DS2-VASc score prior to stroke or TIA Incidence of recurrent stroke or TIA within 12 months. Use and type of oral anticoagulation - percentage of patients who are using OAC drugs at the 12-month follow-up visit.Use of antiarrhythmic drugs - percentage of patients who are using antiarrhythmic drugs at the



12-month follow-up visit.Health Outcome as Evaluated by an EQ-5D Questionnaire - EQ-5D quality of life score,which is a continuous measure of quality of life.

Number of patients 500

Reveal LINQ® and MyCareLink® The Reveal LINQ® Insertable cardiac monitor (ICM) system consists of an insertion kit, the Reveal LINQ® device, and the MyCareLink® patient monitor to permit remote transmission of device data. Dedicated incision and insertion tools facilitate insertion of the device. The device will be inserted in the subcutaneous tissue laterally on the left of the sternal border. Alternatively, over the 4th intercostal space approximately parallel to the sternal border. Electrodes on the ends of the device record ECG signals and an embedded accelerometer measures patient activity.30 31

The AF detection algorithm is based on both an R-R interval and a P-wave evidence score. The P-wave evidence score reduces inappropriate AF detections in the original R-R interval pattern– based algorithm and leverages the evidence of a single P wave between two R waves using morphologic processing of the ECG signal. The AF detection algorithm makes a rhythm classification every 2 minutes. The AF detection algorithm makes rhythm decisions every 2 min. This algorithm has been previously validated against simultaneous Holter monitor data in patients with known AF. Sensitivity was 96.1% for identifying patients with AF and a negative predictive value of 97.4% for correctly excluding the absence of AF.32 33

When an episode is detected at the end of a 2-minute detection period, the first 2 minutes of the ECG from that episode are stored in the device. The device can store up to 14 AF episodes with ECG; afterward, the earliest episode is overwritten by newer episodes. The longest AF episode detected (≥ 10 minutes) is always preserved in memory until a full manual transmission is done. Every night, the ICM wirelessly transmits the last 10 seconds of the 2-minute ECG segment for the longest episode of the day. In addition to the nightly wireless transmissions, the patient can manually transmit the full information on all episodes stored in memory at any given time.

The investigators will be trained in the procedure for insertion of Reveal LINQ® ICM and the use of the CareLink® patient. The investigators will also have access to e-learning programs at www.medtronicacademy.com and they will have access to the CareLink Network pages for monitoring of included patients. In addition the Executive Working Group will serve as a core lab to follow up all the results from the ICM.

Biomarkers NT-proBNP/BNP and Troponins will be analyzed in the laboratories of the participating centers as part of routine clinical practice. Biomarkers will be analyzed at Oslo University Hospital, Firalis SAS, Huningue, France and Østfold Hospital Trust. Olink Technology with Proseek® Multiplex Cardiovascular disease (CVD) will be used to search for predictors of incident AF with reagent kit measuring CVD related human protein biomarkers. The assays on the panels have been selected to focus on high-abundance proteins. The Proseek reagents are based on PEA, a Proximity Extension Assay technology,34, 35where oligonucleotide labelled antibody probe pairs are allowed to bind to their respective target protein present in the sample.



The search for potential biomarkers will also include the following approaches: 1. Measuring inflammatory and related markers in blood collections (using enzyme

immunoassays and multiplex)2. Assessing lncRNA exosome profile in blood collections using LncProfiler qPCR array3. Analyzing mRNA levels in leucocyte populations using qRT-PCR4. To achieve in depth characterization of the inflammatory and fibrotic pathways, we

will perform RNA sequencing analyses of leukocyte subpopulations from bloodsamples

Selection of subjects The patients to be included with cryptogenic ischemic stroke or TIA Inclusion criteria: 5. Cryptogenic ischemic stroke or TIA patients ≤ 10 days from symptom start.6. A stroke/TIA is considered to be cryptogenic if no cause can be determined despite an

extensive workup according to the standard protocol of the participating center. Beforeinclusion to the study, the following tests are required to establish the diagnosis ofcryptogenic stroke or TIA†:

a. Brain MRI or CT†.b. 12-lead ECG for AF detection.c. 24-h ECG monitoring for AF detection and premature atrial complex analysis (e.g.

Holter or telemetry).d. TTE (transthoracic echocardiography).e. TEE (transesophageal echocardiography) in patients aged £ 65 years.f. Colour Duplex ultrasound examination of the pre-cerebral arteries.g. CTA or MRA of head and neck to rule out other causes of stroke.h. Screening for thrombophilia < 50 years of age.

7. Age > 18 years at onset of TIA/stroke.8. A participation consent form signed by the patient or a legally authorized representative.†TIA cases with acute non-lacunar infarct on Diffusion Weighted Imaging are included asTIA events.

Exclusion criteria: 1. Known etiology of TIA or stroke.2. TIA without documented cerebral ischemia on Diffusion Weighted Imaging.3. Untreated hyperthyroidism.4. Myocardial infarction less than 1 month prior to the stroke or TIA.5. Coronary bypass grafting less than 1 month prior to the stroke or TIA.6. Valvular heart disease requiring immediate surgical intervention.7. History of atrial fibrillation or atrial flutter.8. Patent Foramen Ovale (PFO) or PFO where there is or was an indication to start oral

anticoagulation.9. Permanent indication for OAC treatment at enrollment.10. Permanent contra-indication for OAC.11. Life expectancy less than 1 year.12. Pregnancy now or < 3 months.13. An indication for an Implantable Pulse Generator (IPG), Implantable Cardioverter-

Defibrillator (ICD), Cardiac Resynchronization Therapy (CRT) or an implantablehemodynamic monitoring system.



14. Patients otherwise not available for follow-up (e.g. non-resident) or patients withconcurrent disease which may affect clinical outcome (e.g. multiple sclerosis, cancer).

Statistics The NOR-FIB Study is a multi-center prospective observational study designed to detect atrial fibrillation in cryptogenic stroke or TIA with long term ECG monitoring and assessment of biomarkers related to atrial fibrillation. Power calculation. NOR-FIB aims at detecting a 9 % higher percentage of atrial fibrillation with Reveal LINQ® in patients with increased levels of biomarkers related to atrial fibrillation compared to patients with lower biomarker levels and will include 500 patients during a 1.5-year period.

Transport, storage and analyzes of blood samples Routine biochemical analyzes: Troponin T/Troponin-I and NT-proBNP/BNP will be carried out at the participating centers. The remaining blood samples will be stored locally before transport to Oslo University Hospital. The analyses of biomarkers will be carried out at Oslo University Hospital, Østfold Hospital Trust and Firalis Lab in France.

3.2. Roles, organization and cooperation Executive Working Group Dan Atar MD PhD Professor (Leading Cardiologist, Manager), Anne Hege Aamodt MD PhD (Principle Investigator, coordinating the centers, manager of ECRI), Barbara Ratajczak-Tretel, MD (ECG core lab), Anna T. Lambert, MD (ECG core lab), Bente Halvorsen (biomarkers).

The Executive Working Group delivers secretary function for the Steering Committee. The group is responsible for the day-to-day logistics and will serve with secretary function for the steering committee.

Steering committee Anne Hege Aamodt, MD PhD, David Russell, MD PhD Professor, Department of Neurology, Dan Atar, MD PhD Professor, Department of Cardiology, Oslo University Hospital, Oslo. Bente Halvorsen, Dr.Philos Professor, Research Institute of Internal Medicine, Institute of Clinical Medicine, University of Oslo, Else Charlotte Sandset, MD PhD, Department of Neurology, Oslo University Hospital, Oslo. Halvor Næss, MD PhD Professor and Aliona Nacu, MD, Department of Neurology, Haukeland University Hospital, Bergen. Waleed Ganima, MD PhD Associate Professor, Head of Research Center, Østfold Hospital Trust, Kalnes. Christine Jonassen, PhD Professor, Østfold Hospital Trust, Kalnes, The Norwegian University of Life Science, Barbara Ratajczak-Tretel, MD, Department of Neurology, Østfold Hospital Trust, Kalnes. Anna T. Lambert, MD, Department of Neurology, Østfold Hospital Trust, Kalnes. Thomas C. Truelsen, MD PhD, Department of Neurology, Righospitalet University Hospital, Copenhagen. Titto Idicula, MD PhD, Department of Neurology, St. Olav University Hospital, Trondheim. Karen L. Ægidius, Department of Neurology, Bispebjerg University Hospital, Copenhagen. Håkon Tobro, MD, Department of Neurology, Telemark Hospital, Skien. Siv B. Krogseth, MD, Department of Neurology, Vestfold Hospital, Tønsberg. Håkon Ihle-Hansen, MD and Guri Hagberg, MD, Department of Internal Medicine, Vestre Viken Hospital Trust, Bærum Hospital, Bærum. Christina Kruuse, MD PhD, Ass. Professor, Department of Neurology, Herlev Gentofte Hospital, Copenhagen. Rolf Salvesen, MD PhD, Professor, and Mathilde Johnsen, MD, Department of Neurology, Nordlandssykehuset, Bodø. Maja Villseth, MD, Department of Neurology, Drammen Hospital, Vestre Viken Hospital Trust.



The steering committee approves the study protocol and will decide on necessary protocol amendments throughout the study. The steering committee also acts as publishing committee and will supervise the distribution of writing tasks during and after the study period.

Scientific advisory board Mårten Rosenqvist, Karolinska University Hospital, Stockholm, Sweden, Jesper Hastrup Svendsen Rigshospitalet University Hospital, Copenhagen, Denmark and Terje R. Pedersen, University of Oslo, Norway.

The following centers have agreed to participate in the NOR-FIB Study: Site N⁰ Site City Local investigator 1 Haukeland University Hospital Bergen Halvor Næss and Aliona

Nacu 2 Oslo University Hospital,

Ullevål Oslo Else Charolotte Sandset

3 Oslo University Hospital Oslo Anne Hege Aamodt 4 St. Olav University Hospital Trondheim Titto Idicula 5 Østfold Hospital Trust Kalnes Barbara Ratajczak-Tretel 6 Telemark Hospital Skien Håkon Tobro 7 Vestfold Hospital Tønsberg Siv B. Krogseth 8 Bærum Hospital, Vestre Viken

Hospital Trust Bærum Håkon Ihle-Hansen and

Guri Hagberg 9 Nordlandssykehuset Bodø Rolf Salvesen and

Mathilde Johnsen 10 Rigshospitalet University

Hospital Copenhagen Thomas C. Truelsen

11 Bispebjerg University Hospital Copenhagen Karen L. Ægidius 12 Herlev Gentofte Hospital Copenhagen Christina Kruuse 13 Drammen Hospital, Vestre

Viken Hospital Trust Drammen Maja Villseth

14 Molde Hospital, More and Romsdal Hospital Trust

Molde Guttorm Eldøen

Data collection and ECRI (European Cerebrovascular Research Infrastructure) Data will be registered using the webform in the Services for Sensitive Data (TSD) at the University of Oslo. The centers in the NOR-FIB Study are already participating in the research network NORSTROKE which is using the European Cerebrovascular Research Infrastructure (ECRI, www.ecri.no). There are several on-going multicenter trials in ECRI including a randomized controlled trial of acute thrombolytic treatment in acute ischemic stroke (NOR-TEST), the Norwegian Stroke in the Young Study (NOR-SYS II), the Norwegian Intracerebral Hemorrhage Trial (NOR-ICH) and the Norwegian Central Retinal Artery Occlusion and Thrombolysis Study (NOR-CRAOS).

This is an extensive cooperation project between neurologist, cardiologists, geriatricians and basic scientists involving stroke units both in the Nordic countries.

Plan for progress Inclusion period: 18 months Duration of follow-up period: 12 months The first three centers start including patients in December 2016. The inclusion of patients



from the other centers will follow subsequently. More Danish centers and Swedish centers are invited and we are planning to recruit up to 25 centers.

3.3. Plan for milestones, dissemination and publishing The overall project plan is designed to ensure an efficient workflow and stable progress throughout the study period. The inclusion of patients will be started in December 2016. The first delivering of devices from Medtronic to the first stroke units is confirmed. The time schedule for the further delivering of the devices from Medtronic will ensured that the devices will be available at all participating centers. The study has been presented in national and international congresses. The study is registered at www.clinicaltrials.gov and the manuscript describing the protocol and the results from the pilot study are in progress. There will be a close cooperation with user organizations to inform about the results of the study. It will be a defined aim to communicate the results to a broader public.

3.4. Implementation plan The demonstration that known or new cardiovascular biomarkers can be used to identify AF in cryptogenic stroke and TIA patients will have a considerable clinical impact in the management of these patients. The detection methods for some of these biomarkers are already available and they can potentially be immediately used routinely in the clinical assessment of cryptogenic stroke and TIA patients. The detection of new biomarkers will be followed by their commercialization. This project has therefore considerable innovation potential.

3.5. Funding NOR-FIB is an investigator driven academic study. 400 of 500 devices are supported by Medtronic. NOR-FIB will be run by two part-time research fellows (“Østfold Hospital Trust”) and with a postdoctoral researcher (”South Eastern Norway Regional Health Authority”). The study is supported by the research infrastructure of the European Cerebrovascular Research Infrastructure (ECRI).

4. User interactionThe project has considerable user interaction. All the user organisations are informed aboutthe project and will be informed further both in writing and in lectures about the project.Torgeir Solberg Mathisen, health advisor in the stroke organisation National Heart and LungDisease Society is an advisor in the project and will provide information about the study inorder to stimulate recruitment to the study. They will also inform about the results of thestudy.

5. Ethical perspectivesThe project will aim at the highest ethical standards. The Norwegian South-Eastern RegionalEthical Committee has approved this project (2013/2371). The study is also approved by theethics committee in Denmark. All participation will be based on written, informed consent.No personal identification of study subjects will be possible for other researchers than theproject leader and other clinicians directly involved in data collection. The study does notinvolve harm or risk to the participants, except possible minor pain related to insertion of theICM. Each investigational site will be trained with regards to the investigational plan.Investigator/Site Personnel will undergo training prior to performing any study-relatedprocedures. All training must be documented. The health authorities approve the monitoringdevices, which will be used in the study.



6. References1. Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global and regional burden ofstroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet.2014; 383: 245-54.2. Stovner LJ, Hoff JM, Svalheim S and Gilhus NE. Neurological disorders in the GlobalBurden of Disease 2010 study. Acta Neurol Scand Suppl. 2014: 1-6.3. Saver JL. Cryptogenic Stroke. N Engl J Med. 2016; 375: e26.4. Ji R, Schwamm LH, Pervez MA and Singhal AB. Ischemic stroke and transientischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, andthrombolysis. JAMA Neurol. 2013; 70: 51-7.5. Li L, Yiin GS, Geraghty OC, et al. Incidence, outcome, risk factors, and long-termprognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-basedstudy. Lancet Neurol. 2015; 14: 903-13.6. Wolf ME, Grittner U, Bottcher T, et al. Phenotypic ASCO Characterisation of YoungPatients with Ischemic Stroke in the Prospective Multicenter Observational sifap1 Study.Cerebrovasc Dis. 2015; 40: 129-35.7. Bang OY, Ovbiagele B and Kim JS. Evaluation of cryptogenic stroke with advanceddiagnostic techniques. Stroke. 2014; 45: 1186-94.8. Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime riskof atrial fibrillation: the Rotterdam study. Eur Heart J. 2006; 27: 949-53.9. Sposato LA, Cipriano LE, Saposnik G, Ruiz Vargas E, Riccio PM and Hachinski V.Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic reviewand meta-analysis. Lancet Neurol. 2015; 14: 377-87.10. Andrade JG, Field T and Khairy P. Detection of occult atrial fibrillation in patientswith embolic stroke of uncertain source: a work in progress. Frontiers in physiology. 2015; 6:100.11. Glotzer TV and Ziegler PD. Cryptogenic stroke: Is silent atrial fibrillation the culprit?Heart Rhythm. 2015; 12: 234-41.12. Rizos T, Wagner A, Jenetzky E, et al. Paroxysmal atrial fibrillation is more prevalentthan persistent atrial fibrillation in acute stroke and transient ischemic attack patients.Cerebrovasc Dis. 2011; 32: 276-82.13. Aamodt AH, Sandset PM, Atar D, Tveit A and Russell D. [Atrial fibrillation andstroke]. Tidsskr Nor Laegeforen. 2013; 133: 1453-7.14. Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying atrialfibrillation. N Engl J Med. 2014; 370: 2478-86.15. Doliwa PS, Rosenqvist M and Frykman V. Paroxysmal atrial fibrillation with silentepisodes: intermittent versus continuous monitoring. Scandinavian cardiovascular journal :SCJ. 2012; 46: 144-8.16. Ziegler PD, Rogers JD, Ferreira SW, et al. Real-World Experience with InsertableCardiac Monitors to Find Atrial Fibrillation in Cryptogenic Stroke. Cerebrovasc Dis. 2015;40: 175-81.17. Sanders P, Purerfellner H, Pokushalov E, et al. Performance of a new atrial fibrillationdetection algorithm in a miniaturized insertable cardiac monitor: Results from the RevealLINQ Usability Study. Heart Rhythm. 2016; 13: 1425-30.18. Llombart V, Garcia-Berrocoso T, Bustamante A, Fernandez-Cadenas I and MontanerJ. Cardioembolic stroke diagnosis using blood biomarkers. Current cardiology reviews. 2013;9: 340-52.19. Santamarina E, Penalba A, Garcia-Berrocoso T, et al. Biomarker level improves thediagnosis of embolic source in ischemic stroke of unknown origin. Journal of neurology.2012; 259: 2538-45.



20. Wachter R, Lahno R, Haase B, et al. Natriuretic peptides for the detection ofparoxysmal atrial fibrillation in patients with cerebral ischemia--the Find-AF study. PloS one.2012; 7: e34351.21. Seegers J, Zabel M, Gruter T, et al. Natriuretic peptides for the detection ofparoxysmal atrial fibrillation. Open heart. 2015; 2: e000182.22. Fonseca AC, Brito D, Pinho e Melo T, et al. N-terminal pro-brain natriuretic peptideshows diagnostic accuracy for detecting atrial fibrillation in cryptogenic stroke patients.International journal of stroke : official journal of the International Stroke Society. 2014; 9:419-25.23. Beaulieu-Boire I, Leblanc N, Berger L and Boulanger JM. Troponin elevation predictsatrial fibrillation in patients with stroke or transient ischemic attack. J Stroke CerebrovascDis. 2013; 22: 978-83.24. Howlett PJ, Hatch FS, Alexeenko V, Jabr RI, Leatham EW and Fry CH. DiagnosingParoxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia?BioMed research international. 2015; 2015: 910267.25. Wu N, Chen X, Cai T, et al. Association of inflammatory and hemostatic markers withstroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis.The Canadian journal of cardiology. 2015; 31: 278-86.26. Sharp FR, Jickling GC, Stamova B, et al. RNA expression profiles from blood for thediagnosis of stroke and its causes. Journal of child neurology. 2011; 26: 1131-6.27. Jickling GC and Sharp FR. Blood biomarkers of ischemic stroke. Neurotherapeutics :the journal of the American Society for Experimental NeuroTherapeutics. 2011; 8: 349-60.28. Orenes-Pinero E, Montoro-Garcia S, Patel JV, Valdes M, Marin F and Lip GY. Roleof microRNAs in cardiac remodelling: new insights and future perspectives. Int J Cardiol.2013; 167: 1651-9.29. Christensen LM, Krieger DW, Hojberg S, et al. Paroxysmal atrial fibrillation occursoften in cryptogenic ischaemic stroke. Final results from the SURPRISE study. Europeanjournal of neurology : the official journal of the European Federation of NeurologicalSocieties. 2014; 21: 884-9.30. Mittal S, Sanders P, Pokushalov E, et al. Safety Profile of a Miniaturized InsertableCardiac Monitor: Results from Two Prospective Trials. Pacing Clin Electrophysiol. 2015; 38:1464-9.31. Rogers JD, Sanders P, Piorkowski C, et al. In-office insertion of a miniaturizedinsertable cardiac monitor: Results from the Reveal LINQ In-Office 2 randomized study.Heart Rhythm. 2017; 14: 218-24.32. Hindricks G, Pokushalov E, Urban L, et al. Performance of a new leadless implantablecardiac monitor in detecting and quantifying atrial fibrillation: Results of the XPECT trial.Circ Arrhythm Electrophysiol. 2010; 3: 141-7.33. Mittal S, Rogers J, Sarkar S, et al. Real-world performance of an enhanced atrialfibrillation detection algorithm in an insertable cardiac monitor. Heart Rhythm. 2016; 13:1624-30.34. Assarsson E, Lundberg M, Holmquist G, et al. Homogenous 96-plex PEAimmunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One.2014; 9: e95192.35. Lundberg M, Eriksson A, Tran B, Assarsson E and Fredriksson S. Homogeneousantibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood. Nucleic Acids Res. 2011; 39: e102.

FORESPØRSEL OM DELTAKELSE I FORSKNINGSPROSJEKTET

DEN NORDISKE HJERNESLAG OG ATRIEFLIMMER-‐STUDIEN

Dette er et spørsmål til deg om å delta i et forskningsprosjekt for å undersøke forekomsten av hjerterytmeforstyrrelser ved hjerneslag hvor årsaken ikke avklares ved standard utredning. Du blir spurt om deltakelse i denne studien fordi du har fått et slikt hjerneslag hvor årsaken til blodproppen er usikker.

Ved en betydelig andel av hjerneslagene avdekkes ikke årsaken til blodproppen til tross for grundig utredning. Atrieflimmer er den vanligste hjerterytmeforstyrrelsen i befolkningen og er årsaken til 1/3 av slagtilfellene med kjent årsak. Men i tillegg er atrieflimmer trolig også årsaken til minst like stor andel av slagtilfellene der årsaken ikke avdekkes ved standard utredning. Etter som atrieflimmer ofte bare opptrer anfallsvis og ikke trenger å gi symptomer, kan tilstanden være krevende å avdekke.

HVA INNEBÆRER PROSJEKTET?

Å delta i denne studien innebærer at det blir samlet inn opplysninger fra din journal og tatt blodprøver i forbindelse med at du er innlagt på grunn av hjerneslaget. Du vil deretter få satt inn en liten hjerterytmeregistrator som skal registrere hjerterytmen din i ett år. Hjerterytmeregistratoren veier 2,5 gram og måler 44,8 mm x 7,2 mm x 4,0 mm. Den legges inn under huden på brystkassen ved en enkel prosedyre som utføres av lege eller sykepleier.

Etter at du har fått lagt inn hjerterytmeregistratoren vil du bli innkalt til 3 polikliniske kontroller – ved 3 og 6 måneder samt ett år. På ett års-‐kontrollen vil det bli tatt blodprøver. Ved de øvrige kontrollene vil det kun være en konsultasjon som varer 30-‐60 minutter. Ved alle kontrollene avleses hjerterytmeregistratoren. Dersom det påvises atrieflimmer, vil medisineringen bli justert i forhold til det. Det er slagleger ved sykehuset hvor du har vært innlagt som vil følge deg gjennom dette året. Det er vanlig med poliklinisk kontroll 3-‐måneder etter hjerneslaget. Deltakelse i denne studien vil altså innebære at du kommer til to ekstra kontroller.

Oslo universitetssykehus er ansvarlig for studien.

The Nordic Atrial Fibrillation and Stroke Study – NOR-‐FIB-‐studien. 1.12.2015, versjon 1.0 Side 2 / 4

MULIGE FORDELER OG ULEMPER

Fordelene ved å delta i dette prosjektet er at du får ekstra grundig oppfølging for hjerterytmeforstyrrelser som kan være årsaken til hjerneslaget du har fått og at medisineringen din blir optimalisert. Deltakelse innebærer at du får satt inn en hjerterytmeregistrator under huden. Selve innsettingsprosedyren medfører kortvarig og lett ubehag, men du vil ikke ha noe ubehag ved å ha hjerterytmeregistratoren under huden videre gjennom studien som varer ett år. Det er ikke noen spesiell risiko ved å ha en slik hjerterytmeregistrator under huden og den gir ingen spesielle begrensninger i din livsutfoldelse.

FRIVILLIG DELTAKELSE OG MULIGHET FOR Å TREKKE SITT SAMTYKKE

Det er frivillig å delta i prosjektet. Dersom du ønsker å delta, undertegner du samtykkeerklæringen på siste side. Du kan når som helst og uten å oppgi noen grunn trekke ditt samtykke. Dette vil ikke få konsekvenser for din videre behandling. Dersom du trekker deg fra prosjektet, kan du kreve å få slettet innsamlede prøver og opplysninger, med mindre opplysningene allerede er inngått i analyser eller brukt i vitenskapelige publikasjoner. Dersom du senere ønsker å trekke deg eller har spørsmål til prosjektet, kan du kontakte overlege Anne Hege Aamodt, telefon 02770, epost: anhaam@ous-‐hf.no.

HVA SKJER MED INFORMASJONEN OM DEG?

Informasjonen som registreres om deg skal kun brukes slik som beskrevet i hensikten med studien. Du har rett til innsyn i hvilke opplysninger som er registrert om deg og rett til å få korrigert eventuelle feil i de opplysningene som er registrert.

Alle opplysningene vil bli behandlet uten navn og fødselsnummer eller andre direkte gjenkjennende opplysninger. En kode knytter deg til dine opplysninger gjennom en navneliste.

Prosjektleder har ansvar for den daglige driften av forskningsprosjektet og at opplysninger om deg blir behandlet på en sikker måte. Informasjon om deg vil bli anonymisert eller slettet senest fem år etter prosjektslutt.


HVA SKJER MED PRØVER SOM BLIR TATT AV DEG?

Prøvene som tas av deg skal oppbevares i en forskningsbiobank ved Nevrologisk avdeling ved Oslo universitetssykehus før de analyseres. Ansvarshavende for biobanken er overlege Mona Skjelland. Biobanken varer til 01.01.2030.

BLODPRØVER INKLUDERT GENETISKE UNDERSØKELSER

Blodprøvene som tas av deg analyseres med tanke på atrieflimmer. Det skal gjøres analyse av hjertemarkører (proteiner og peptider) og betennelsesstoffer som kan være forhøyet ved atrieflimmer. I disse prøvene inngår det også enkelte genanalyser (RNA, ribonukleinsyrer). Disse resultatene kan bidra til å styrke holdepunktene for atrieflimmer og at blodproppen kommer fra hjertet. På sikt vil denne typen blodprøver trolig kunne bidra til å avdekke årsaken til hjerneslag.

FORSIKRING

Du er forsikret gjennom pasientskadeloven.

GODKJENNING

Prosjektet er godkjent av Regional komite for medisinsk og helsefaglig forskningsetikk 2013/2371.


SAMTYKKE TIL DELTAKELSE I PROSJEKTET

JEG ER VILLIG TIL Å DELTA I PROSJEKTET

Sted og dato Deltakers signatur

Deltakers navn med trykte bokstaver

Stedfortredende samtykke

Som nærmeste pårørende til _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ (Fullt navn) samtykker jeg til at hun/han kan delta i prosjektet.

Sted og dato Pårørendes signatur

Pårørendes navn med trykte bokstaver

Jeg bekrefter å ha gitt informasjon om prosjektet

Sted og dato Signatur

Rolle i prosjektet

Vigdis Bjerkeli, [email protected], Research Institute for Internal Medicine (RIIM), Oslo University Hospital, Rikshospitalet, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo.

Page 1 of 1

Blood sampling and pre-‐‑analytical treatment of blood samples

Standard Operating Procedure (SOP), Appendix 2

1. Vacutainer® Blood Collection Tubes:• 3 x serum tube VACUETTE® TUBE 6 ml Z Serum Clot Activator red cap-‐black ring, non-‐ridged

(plastic | glass)• 2 x tube EDTA Plasma VACUETTE® TUBE 3 ml K2E K2EDTA 13x75 lavender cap-‐black ring,

PREMIUM• 1 x tube Citrate Tubes. solution. VACUETTE® TUBE 3.5 ml 9NC Coagulation sodium citrate

3,8% blue cap — black ring

2. What is done immediately after blood collection?• Serum tubes at room temperature. (Red cap)• EDTA tubes inserted on ice. (Lavender cap)• Citrate tube on ice. (Blue cap)

3. Processing in the laboratory• EDTA tubes and citrate tubes centrifuge at (2500crf) in 20 min 4oC within 30 minutes of

plasma (yellow liquid). Stored in Nunc tubes at -‐80 ° C.• Serum tubes stands until coagulation but a maximum of 2 hours. Then centrifugation for 10

minutes (2500crf) at Room Temp. Stored in Nunc tubes at -‐80 ° C.

4. Storage• Serum (yellow liquid) distributed in Nunc tubes with red cap.• EDTA plasma (yellow liquid) stored in Nunc tubes with purple cap.• Citrate plasma (yellow liquid) is stored in Nunc tubes with blue cap.• The tubes are marked with numbers and the date on tubes.

1

Technical Guide to Echocardiography Prepared by: Thomas von Lueder. Version: 1.0 (November 2016)

General remarks: Participants who meet the entry criteria (see protocol) will undergo standard transthoracic (TTE) and transesophageal (TEE) echocardiography. The aim of the echocardiogram is a thorough assessment of left ventricular systolic and diastolic function and any underlying pathology. TEE is requested to exclude underlying anatomical causes of stroke such as persisting foramen ovale (PFO), septal defects among others. A well-‐defined ECG signal should be obtained and body weight and height must be entered prior to the commencement of the study.

Imaging Protocol Guidelines: Transthoracic echocardiography TTE: The recommendations correspond to what is common (“real world”) practice in many echocardiography laboratories. 1. For each patient 3 good quality cycles should be recorded with sufficient gain to define the endocardium in

all cardiac segments. Do not include ectopic beats if possible and avoid post ectopic beats.2. For patients with arrhythmia 5 good quality cycles should be obtained.3. The gain should remain the same for all cycles.4. Spectral Doppler recording should be performed at 50 mm/second.5. Apical views for the assessment of the left ventricular volumes and ejection fraction should all be acquired

with the same gain setting; special care should be taken to avoid foreshortening of the apex.6. Apical views for the Doppler assessment of mitral valve inflow should be acquired with care to avoid

apical foreshortening. Quantitative measurements of the LV volume, mass and function will be made andthus good quality endocardial resolution is important.

7. Doppler images should be made immediately following the 2D image within each view.8. Apical two-‐chamber views should enable tracing of ventricular and atrial internal borders.

Imagining view sequences − the following sequences should be obtained: 1. Parasternal long-‐axis view (2D, M-‐mode, Doppler)2. Parasternal short-‐axis view at the mitral valve level (2D).3. Parasternal short-‐axis view at the tricuspid and aortic valve level (2D, Doppler, CW).4. Parasternal short-‐axis view at the papillary muscle level (2D).5. Parasternal short-‐axis view at the apical level (2D).6. Apical four-‐chamber view (2D, Doppler, M-‐mode for TAPSE+MAPSE).7. Apical five-‐chamber view (2D, Doppler).8. Apical two-‐chamber view (2D).9. Apical long-‐axis view (three-‐chamber) (2D, Doppler).10. Subcostal views (2D, Doppler).

Summary of echocardiographic examination and criteria for systolic and diastolic dysfunction. Measurements will be taken according to the guidelines from the American Society of Echocardiography. 1. Left ventricle cavity size, septal and posterior wall dimensions and fractional shortening using M-‐mode

from the para-‐sternal long axis view. Also measure left atrial and sinus Valsalva dimension using M-‐mode.

2. Left ventricular ejection fraction estimated using a biplane disc summation method (Simpson’s method).3. Doppler measurements of transpulmonary flow (CW Doppler), peak flow retrograde tricuspid

regurgitation (CW; only if TR is present), transmitral flow (PW), LVOT (PW) and transaortic flow (CW)4. Diastolic function will be estimated as follows:

a. pulse wave Doppler of the mitral valve inflow to calculate E/A ratio and deceleration time alongwith change in E/A ratio

b. septal and lateral mitral annuli tissue velocity using pulse wave tissue Doppler from the apicalwindow, with E/E’ ratio being calculated;

2

c. pulse wave Doppler of the pulmonary vein.d. pulse wave tissue Doppler of tricuspid annulus (peak systole, “S”)

5. Left atrial volume from planimetered apical four and two chamber views.6. Longitudinal shortening will be assessed by M-‐mode of tricuspid (“TAPSE”) and septal plus lateral mitral

valve plane (“MAPSE”)

Systolic dysfunction Systolic function will be classified according to the left ventricular EF (EF ≤40% reduced; EF 41-‐49% mid-‐range; EF ≥50% preserved), following current ESC guidelines on heart failure. Other suitable parameters of systolic function will be assessed.

Diastolic dysfunction Diastolic function will be assessed and categorized, as previously described and validated, normal; mild dysfunction (impaired relaxation without evidence of increased filling pressures); moderate dysfunction (impaired relaxation with moderate elevation of filling pressures or pseudo normal filling); severe dysfunction (advanced reduction in compliance or restrictive filling). Two Doppler criteria will be required for classification of moderate and severe dysfunction, Participants with only one Doppler criterion or borderline criteria will be classified as intermediate.

Transesophageal echocardiography (TEE) All study participants aged £ 65 years need to undergo TEE exam. TEE should be performed according to local protocol and practice guidelines. In order to rule out any shunt (PFO, ASD, VSD), we encourage focused color Doppler assessment of the atrial septum employing Valsalva maneuver. If no shunt is visualized, we require bolus injection of agitated saline using Valsalva maneuver. Care has to be taken to optimize contrast density at the fossa ovalis, by raising the arm immediately after bolus injection. Significant shunt is defined as microbubbles visualized in the left atrium within 4 cardiac cycles, after Valsalva, or as typical right atrial contrast defect. If in doubt repeat the bolus injection. All valves should be thoroughly examined using native and color Doppler views at identical positions. The aortic rot as well as the descending thoracic aorta may reveal thrombi and other pathology with relevance to stroke, and should therefore be visualized as well. In general, we recommend to do a complete examination whenever performing TEE.

Glossary of common terms and variables AV valves – atrioventricular valves CFD – colour flow Doppler CRF – case report form CW – continuous wave 2D – two-‐ dimensional ECG – electrocardiogram Hz – hertz IVC – inferior vena cava LA – left atrium LV – left ventricle

LVOT – left ventricular outflow tract PW – pulse wave RA – right atrium RV – right ventricle RVOT – right ventricular outflow tract RVSP – right ventricular systolic pressure PISA – proximal isovolumetric surface area TDI – tissue Doppler imaging TGC – time gain compensation

References Available upon request

Appendix 4 - Insertion of Reveal LINQ® and follow-up by CareLink

Extra information from Medtronic

Insertion of Reveal LINQ® Reveal LINQ® with its weighs of 2,5 g and measures of 7x45x4 mm (1). Device miniaturization, simplified insertion procedure and enhanced automation vastly increase physician and patient acceptance (2).

The Reveal LINQ® ICM system consists of an insertion kit, the Reveal LINQ® device, Patient Assistant Device and My CareLink® patient monitor to permit remote transmission of device data (1, 2).

Reveal LINQ® is inserted subcutaneously with a sterile procedure. The technique of device insertion is facilitated by dedicated incision and insertion tools with the ICM preloaded, assists in the creation of the pocket and placement of the device (1). The device is implanted at the fourth intercostal space, 2 cm from the border of the sternum and at 45 degrees angle to the plane of the sternum with the incision cranial to the device. There are more alternatives for possible insertion of the device including parallel sternal and 90 degrees’ insertion, but the first one is evaluated as the best one (2). There is no need for conscious sedation under the procedure but applying of local anesthesia is recommended. The skin incision can be closed using adhesive glue or surgical tape without the need of suture, but this is optional. Device sensing is performed before incision closure and if it is not acceptable, the device can be retrieved and repositioned to locate a position with acceptable sensing (2).

The insertion of the device is traditionally done in electrophysiology laboratory but can safely be performed outside of the cardiac laboratory following rules of sterile procedure and recommendations for insertion given by producer of the device (3). Clinical trials using older types of ICM shows that in-office device insertion can be accomplished with a high level of patient and physician satisfaction and comparable adverse event rates while expediting diagnosis (4). It represents a reasonable alternative to the in-hospital setting (5).

Producer claims there are no contraindications for insertion of Reveal LINQ device, however, the patient`s particular medical condition may dictate whether or not a subcutaneous, chronically implanted device can be tolerated. Potential adverse events following device placement are device rejection, migration of the device, infection and erosion through the skin (6). In one clinical trial implantation site pain also occurred (7).

Abbreviations: ICM - insertable cardiac monitor

References: 1. Ziegler PD, Rogers JD, Ferreira SW, et al. Real-World Experience with Insertable Cardiac Monitors to Find Atrial Fibrillation inCryptogenic Stroke. Cerebrovascular diseases. 2015; 40: 175-81.2. Tomson TT and Passman R. The Reveal LINQ insertable cardiac monitor. Expert review of medical devices. 2015; 12: 7-18.3. Wong GR, Lau DH, Middeldorp ME, et al. Feasibility and safety of Reveal LINQ insertion in a sterile procedure room versuselectrophysiology laboratory. International journal of cardiology. 2016; 223: 13-7.4. Pachulski RT, Cockrell J, Rogers J, et al. Reveal in-office study. Arrhytmias. 2012; 59: E648-E.5. Pachulski R, Cockrell J, Solomon H, Yang F and Rogers J. Implant evaluation of an insertable cardiac monitor outside theelectrophysiology lab setting. PloS one. 2013; 8: e71544.6. Medtronic. REVEAL LINQ™ LNQ11 Insertable Cardiac Monitor, Clinician Manual. 2015.7. Purerfellner H, Sanders P, Pokushalov E, Di Bacco M, Bergemann T and Dekker LR. Miniaturized Reveal LINQ insertablecardiac monitoring system: First-in-human experience. Heart rhythm : the official journal of the Heart Rhythm Society. 2015; 12: 1113-9.

INSERTABLE CARDIAC MONITOR

Insertion ProcedureQuick Reference Card

Note: For optional insertion locations and the detailed insertion procedure, refer to the Reveal LINQ Clinician Manual.

Pinch the skin and make an incision with the supplied incisiontool.

Recommended subcutaneous

insertion location

1 Best

2 Good

Pinch the skin and insert the supplied insertion tool completely to create a tunnel approximately 8 mm under the skin.

Rotate the insertion tool 180 degrees once to open the incision for inserting the cardiac monitor.

Insert the supplied plunger to push the preloaded monitor completely into the pocket. When the plunger is completelypushed in, the monitor is fully inserted.

Pinch at the incision site to hold the monitor in place (approximately 10 mm away from the incision) and then remove the plunger and the insertion tool.

www.medtronic.com

ManufacturerMedtronic, Inc.710 Medtronic ParkwayMinneapolis, MN 55432USA+1 763 514 4000

AuthorizedRepresentative in the European CommunityMedtronic B.V.Earl Bakkenstraat 106422 PJ HeerlenThe Netherlands+31 45 566 8000

Europe/MiddleEast/AfricaMedtronic InternationalTrading SàrlRoute du Molliau 31Case Postale 84CH-1131 TolochenazSwitzerland+41 21 802 7000AustraliaMedtronic Australasia PtyLtd97 Waterloo RoadNorth Ryde, NSW 2113Australia

CanadaMedtronic of Canada Ltd99 Hereford StreetBrampton, Ontario L6Y 0R3Canada+1 905 460 3800Technical manualswww.medtronic.com/manuals

*M955763A001*© Medtronic, Inc. 2013M955763A001A2013-10-31

Note: For optional insertion locations and the detailed insertion procedure, refer to the Reveal LINQ Clinician Manual.

Recommendedsubcutaneous

insertion location

1 Best

2 Good

Pinch the skin and insert the supplied insertion tool completely to create a tunnel approximately 8 mm under the skin.

Pinch the skin and make an incision with the supplied incision tool.

Rotate the insertion tool 180 degrees once to open the incision for inserting the cardiac monitor.

Insert the supplied plunger to push the preloaded monitor completely into the pocket. When the plunger is completely pushed in, the monitor is fully inserted.

Pinch at the incision site to hold the monitor in place (approximately 10 mm away from the incision) and then remove the plunger and the insertion tool.

Insertion Procedure Quick Reference Card

For registering the patient in CareLink go to: europe.medtroniccarelink.net/Clinician/home.asp

and log in with the User ID and Password that you have got from the project manager Anne Hege Aamodt.

Locate device: Place programming head over the Reveal LINQ Insertable Cardiac Monitor (ICM).

Interrogate: Press Find Patient … device interrogation will begin automatically and the Quick Look™ screen will be displayed.

Presenting rhythm/rate: Review live rhythm and evaluate device sensing. Use ECG Reveal and Marker Channel™ to evaluate presenting rhythm and confirm appropriate device sensing.

For more detailed information regarding device sensing, please refer to the Reveal LINQ ICM Clinician Manual.

Quick Look: Review the Quick Look screen.

• Battery Status

• Parameter Settings

Observations/Diagnostics:

From Quick Look screen review the following:

• Observations: Select toreview significant event(s).Press chevron toview more details.

• Print and review RateHistograms, AT/AF Summary,and Cardiac Compass®reports. Select Reports onthe right hand icon menu.

All patient and clinical data are fictitious and for demonstration purposes only.

New Episodes: Review Arrhythmia Episodes.

a. Click Episodes on the right hand icon menuof the programmer screen.

b. Select desired episode type for viewing.

c. View data for a specific episode by selecting theepisode.

d. View episode details by selecting the desired option:Interval Plot, ECG, or Text (text is only available forauto activated).

e. Use the arrows to zoom in the ECG tracingand enhance viewing of ECG rhythm.

Programming and Print as required:

a. Make any necessary programming changes.

b. Print “Changes This Session” and final report. Click on Session icon, and then select “Changes this Session”.

c. Save to Media.

If you have additional questions in the United States, please call technical services at 1 (800) 505-4636.

All patient and clinical data are fictitious and for demonstration purposes only.

EuropeMedtronic International Trading Sàrl.Route du Molliau 31Case postaleCH-1131 Tolochenazwww.medtronic.euTel: +41 (0)21 802 70 00Fax: +41 (0)21 802 79 00

United Kingdom/IrelandMedtronic LimitedBuilding 9Croxley Green Business ParkHatters LaneWatfordHerts WD18 8WWwww.medtronic.co.uk Tel: +44 (0)1923 212213Fax: +44 (0)1923 241004

www.medtronic.eu

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Brief StatementSee the device manual for detailed information regarding the implant procedure, indications, contraindications, warnings, precautions, and potential adverse events.

Duration and rate of automatically detected events

Marker Channel annotations indicate sensing, detection, and interval values.

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ORI

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SMA

LL. S

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TED

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FOLL

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GU

IDE

REVE

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INSE

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CARD

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NO

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Ove

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Reve

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INQ

Mod

el L

NQ

11

Episo

de D

etec

tion

Paus

e, B

rady

, Tac

hy, A

T/AF

, AF

Onl

yLo

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ity36

Mon

ths

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nt A

ssist

ant

Mod

el P

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iagn

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piso

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piso

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AT/A

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Card

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Com

pass

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nds

Rate

Hist

ogra

ms

MRI

Com

patib

ility

Yes,

MR

Cond

ition

al*

Rem

ote

Follo

w-U

pYe

s, M

edtr

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Car

eLin

k® C

ompa

tible

* The

Rev

eal L

INQ

ICM

has

bee

n de

mon

stra

ted

to p

ose

no k

now

n ha

zard

s in

a sp

ecifi

ed M

R en

viro

nmen

t with

spec

ified

co

nditi

ons o

f use

. Ple

ase

see

Reve

al L

INQ

ICM

Clin

icia

n M

anua

l for

mor

e de

tails

.

Reve

al L

INQ

Inse

rtab

le C

ardi

ac

Mon

itor (

ICM

)

4

hO

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S TO

RED

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REVE

AL

L IN

Q™

ICM

A

DD

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L D

I Ag

NO

STIC

S

SYST

EMS

OV

ERV

IEW

To u

se th

e Pa

tient

Ass

ista

nt

1. W

hen

you

expe

rienc

e a

sym

ptom

, pre

ssan

d re

leas

e th

e bu

tton

. The

sear

chin

g lig

htw

ill st

art t

o fla

sh b

lue.

2. Q

u ick

ly h

old

the

Patie

nt A

ssist

ant f

lat

agai

nst y

our c

hest

, dire

ctly

ove

r you

rRe

veal

LIN

Q IC

M.

3. W

hen

a sy

mpt

om is

succ

essf

ully

mar

ked,

the

succ

ess t

one

will

soun

d an

d th

esu

cces

s lig

ht w

ill il

lum

inat

e gr

een.

If th

esu

cces

s sig

nals

do n

ot o

ccur

with

in15

seco

nds,

repe

at st

eps 1

-2.

It’s r

ecom

men

ded

for t

he p

atie

nt to

carr

y th

e Pa

tient

Ass

istan

t at a

ll tim

es.

Und

erst

andi

ng th

e Pa

tient

Ass

ista

nt:

Reco

rd S

ympt

om b

utto

n: P

atie

nt p

ress

es

butt

on to

reco

rd E

CG w

hen

sym

ptom

atic

Sear

chin

g Li

ght:

Flas

hes b

lue

indi

catin

g th

e pa

tient

shou

ld h

old

the

Patie

nt A

ssist

ant

over

the

Reve

al L

INQ

ICM

Succ

ess

Ligh

t: Illu

min

ates

gre

en w

hen

the

sym

ptom

is su

cces

sful

ly m

arke

d

Conn

ectio

n Sl

ot: A

llow

s pat

ient

to c

onne

ct

the

Patie

nt A

ssist

ant t

o a

key

chai

n, la

nyar

d,

or o

ther

per

sona

l ite

m

Patie

nt A

ssis

tant

Succ

ess

Ligh

t (gr

een)

Sear

chin

g Li

ght (

blue

)

Reco

rd S

ympt

om b

utto

n

Conn

ectio

n Sl

ot

Patie

nt A

ssis

tant

Mod

el P

A960

00

5

hO

ME

FOLL

OW

-UP

TRO

UbL

E Sh

OO

TIN

g

STO

RED

EP I

SOD

ES

REVE

AL

LIN

Q™

ICM

A

DD

ITIO

NA

L D

IAg

NO

STIC

S

SYST

EMS

OV

ERV

IEW

Up

to 3

0 m

inut

es o

f pat

ient

-act

ivat

ed e

piso

des

4 e

piso

des @

7.5

min

. eac

h

3 ep

isode

s @ 1

0 m

in. e

ach

2 ep

isode

s @ 1

5 m

in. e

ach

27 m

inut

es o

f aut

omat

ical

ly d

etec

ted

epis

odes

Epis

ode

type

s: Pa

use,

bra

dy, T

achy

• Up

to 2

7 ep

isode

s: 30

seco

nds o

f ECG

dat

a re

cord

ed b

efor

e de

tect

ion

and

up to

27

seco

nds p

rior t

o th

e en

d of

the

episo

de

Atr

ial e

piso

des:

AT/

AF

• Tw

o m

inut

es (i

nclu

ded

in th

e 27

min

utes

of a

utom

atic

ally

de

tect

ed e

piso

des)

of E

CG d

ata

reco

rded

bef

ore

dete

ctio

n

Not

e: T

wo

min

utes

of l

onge

st A

F ep

isod

e st

ored

sinc

e la

st in

terr

ogat

ion

in a

dditi

on to

the

27 m

inut

es o

f aut

omat

ical

ly d

etec

ted

epis

odes

.

30 se

c27

sec

Auto

mat

ic D

etec

tion

End

of e

piso

de

ECg

Dat

a St

orag

e: 5

9 M

inut

es T

otal

6.5

min

1 m

inPa

tient

act

ivat

ion

9 m

in1

min

Patie

nt a

ctiv

atio

n

14 m

in1

min

Patie

nt a

ctiv

atio

n 2 m

inAu

tom

atic

det

ectio

n

6

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ME

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-UP

TRO

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OO

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STO

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EP I

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REVE

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LIN

Q™

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NO

STIC

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OV

ERV

IEW

Auto

-Inte

rrog

atio

n

1. Pl

ace

the

prog

ram

min

g he

adov

er th

e Re

veal

LIN

Q™

ICM

inse

rtio

n sit

e.

2. Pr

ess F

ind

Patie

nt…

Inte

rroga

tion

will

aut

omat

ical

ly b

egin

and

the

Qui

ck L

ook™

scre

en w

ill b

e di

spla

yed.

Not

e:

At in

itial

inte

rroga

tion,

the

prog

ram

mer

re

ads d

ata

colle

cted

by

the

devi

ce si

nce

th

e la

st p

atie

nt se

ssio

n. To

retr

ieve

in

form

atio

n fro

m p

rior f

ollo

w-u

ps,

inte

rroga

te th

e de

vice

aga

in b

y pr

essin

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terr

ogat

e… a

nd se

lect

All.

Star

ting

a Pa

tient

Ses

sion

Usin

g th

e M

edtr

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mer

All p

atie

nt a

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linic

al d

ata

are

fictit

ious

and

for

dem

onst

ratio

n pu

rpos

es o

nly.

7

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SYST

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OO

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Qui

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Revi

ew th

e fo

llow

ing:

Pres

entin

g Rh

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/Rat

e:U

se E

CG R

evea

l® IC

M a

nd M

arke

r Ch

anne

l™ to

eva

luat

e pr

esen

ting

rhyt

hm a

nd d

evic

e se

nsin

g.

batt

ery

Stat

us (s

ee n

ext p

age

for m

ore

info

rmat

ion)

.

Epis

odes

:Sh

ows e

piso

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y ty

pe si

nce

last

pat

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sess

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Para

met

er S

ettin

gs:

Show

s cur

rent

sett

ing

deta

ils

by e

piso

de ty

pe.

Obs

erva

tions

:D

iagn

ostic

dat

a ob

serv

atio

ns re

port

not

able

ar

rhyt

hmia

epi

sode

s. O

ther

obs

erva

tions

in

clud

e st

orag

e or

dev

ice

stat

us in

form

atio

n (fo

r exa

mpl

e, w

hen

the

devi

ce is

app

roac

hing

Re

com

men

ded

Repl

acem

ent T

ime

[RRT

]).

View

ing

the

Colle

cted

Dat

a

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

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purp

oses

onl

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= P

ress

che

vron

for m

ore

deta

iled

info

rmat

ion.

8

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ME

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EP I

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The

batt

ery

can

be:

•goo

d

• RRT

(Rec

omm

ende

d Re

plac

emen

t Tim

e)Fr

om th

e RR

T da

te o

nwar

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9% o

f the

Rev

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devi

ces h

ave

suffi

cien

t bat

tery

cap

acity

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erat

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r at l

east

30

days

bef

ore

the

batt

ery

reac

hes t

he E

nd o

f Ser

vice

(EO

S) st

atus

. To

obta

in a

ll dia

gnos

tic d

ata,

the

devi

ce sh

ould

be

inte

rroga

ted

prio

r to

EOS.

For

con

tinue

dm

onito

ring,

repl

ace

the

devi

ce p

rior t

o EO

S.

• EO

S (E

nd o

f Ser

vice

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mov

e de

vice

. Rep

lace

as n

eede

d.

batt

ery

Stat

us

9

hO

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STO

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EP I

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REVE

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LIN

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NO

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Mar

ker C

hann

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Ann

otat

ions

Mar

ker

Expl

anat

ion

VS

Vent

ricul

ar se

nse

AD

Asys

t ole

det

ectio

n (m

arks

the

first

eve

nt in

a d

etec

ted

paus

e ep

isode

)

B Br

ady

sens

e

BD

Brad

y de

tect

ion

(mar

ks th

e fir

st e

vent

in a

det

ecte

d br

ady

episo

de)

TS

VT (T

achy

) sen

se

TD

VT (T

achy

) det

ectio

n (m

arks

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first

eve

nt in

a d

etec

ted

VT e

piso

de)

(bel

ow th

e ba

selin

e)

FS

FVT

(Tac

hy) s

ense

FD

FVT

(Tac

hy) d

etec

tion

(mar

ks th

e fir

st e

vent

in a

det

ecte

d FV

T ep

isode

)

(bel

ow th

e ba

selin

e)

∆ Pa

tient

-act

ivat

ed sy

mpt

om (o

nly

mar

ked

in E

CG re

cord

ings

stor

ed w

ith th

e Pa

tient

Ass

istan

t)

VS

Igno

red

even

t – a

n ev

ent t

hat e

nds a

noi

se in

terv

al

AD

Asys

t ole

reje

ctio

n (m

arks

a p

ause

that

is d

eter

min

ed to

not

be

asys

tole

)*

FD

FVT

(Tac

hy) r

ejec

tion

(mar

ks a

n ev

ent t

hat w

ould

hav

e be

en d

etec

ted

as F

VT b

ut w

as re

ject

ed d

ue to

noi

se)

TD

AT d

etec

tion

(mar

ks th

e en

d of

at l

east

2 m

inut

es o

f atr

ial a

rrhy

thm

ia)

(abo

ve th

e ba

selin

e)

FD

AF

dete

ctio

n (m

arks

the

end

of a

t lea

st 2

min

utes

of a

tria

l arr

hyth

mia

)

(abo

ve th

e ba

selin

e)

*If m

ore

than

one

eve

nt o

ccur

s dur

ing

a re

fract

ory

perio

d, th

e in

terv

al is

cla

ssifi

ed a

s a n

oise

inte

rval

.

10

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Arrh

ythm

ia E

piso

des

View

ing

the

Colle

cted

Dat

a

Not

e: D

urin

g a

regu

lar f

ollo

w-u

p, it

is n

ot n

eces

sary

to c

lear

the

colle

cted

dat

a, b

ecau

se th

e ol

dest

stor

ed e

piso

des a

re

over

writ

ten

by n

ewer

epi

sode

s whe

n th

e de

vice

mem

ory

is fu

ll.

1. En

ter t

he d

ata

scre

enby

sele

ctin

g th

eEp

isode

s ico

n.

2. Se

lect

des

ired

episo

dety

pes f

or v

iew

ing.

3. Vi

ew d

ata

deta

ils o

f eac

hep

isode

by

sele

ctin

g th

eep

isode

num

ber i

n th

e lo

g.4.

View

epi

sode

det

ails

byse

lect

ing

desir

ed o

ptio

n:In

terv

al P

lot,

ECG

, or T

ext

deta

ils.

5. Ve

rify

appr

opria

te se

nsin

gan

d de

tect

ion

usin

g th

eM

arke

r Cha

nnel

™ A

nnot

atio

ns.2.

3.

4.

5.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.

11

hO

ME

SYST

EMS

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RVIE

W

TRO

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ESh

OO

TIN

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S TO

RED

EPI

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ES

REVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

FOLL

OW

-UP

To v

iew

epi

sode

det

ails:

View

ing

Episo

de D

etai

ls

1. U

se th

e Pl

ot, E

CG, a

nd T

ext o

ptio

nbu

tton

s to

disp

lay

the

sele

cted

episo

de d

ata

in o

ne o

f the

avai

labl

e fo

rmat

s.2.

The

Mar

ker C

hann

el™

disp

lays

the

anno

tate

d ev

ents

. (Se

epa

ge 11

for a

nnot

atio

n le

gend

.)3.

The

Dec

ision

Cha

nnel

disp

lays

an a

nnot

atio

n if

an e

piso

de is

dete

cted

.4.

Use

the

Inte

rval

opt

ion

tosw

itch

betw

een

Inte

rval

(ms)

and

Rate

(bpm

).

1.

2.

3.

4.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.

12

hO

ME

SYST

EMS

OVE

RVIE

W

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Ub L

ESh

OO

TIN

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S TO

RED

EPI

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ES

REVE

AL

L IN

Q™

ICM

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DD

ITIO

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L D

I Ag

NO

STIC

S

FOLL

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-UP

To v

iew

long

est A

F Ep

isode

, sel

ect

Sort

ed b

y; th

en se

lect

D

urat

ion

in th

e dr

op-

dow

n m

enu.

View

ing

Mul

tiple

AT/

AF E

piso

des

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for

dem

onst

ratio

n pu

rpos

es o

nly

13

REVE

AL

LIN

Q™

ICM

A

DD

ITIO

NA

L D

IAg

NO

STIC

S

TRO

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OO

TIN

g

STO

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EPI

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ES

SYST

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OVE

RVIE

W

hO

ME

FOLL

OW

-UP

To a

djus

t and

cus

tom

ize

ECg

sto

rage

Prog

ram

min

g EC

g S

tora

ge fo

r AF

Epi

sode

s

1.Se

lect

AT/

AF D

etec

tion.

2.Se

lect

AT/

AF R

ecor

ding

Thre

shol

d.3.

Sele

ct a

min

imum

leng

th fo

r ECG

stor

age.

No

ECG

will

be

stor

ed fo

rep

isode

s sho

rter

than

the

prog

ram

med

par

amet

ers.

NO

TES:

•T

he d

evic

e au

tom

atic

ally

stor

es o

ne a

dditi

onal

epi

sode

log

data

and

ECG

, the

long

est A

F ep

isode

• The

reco

rds o

f all

AF e

piso

des w

ill b

e st

ored

in th

e Ca

rdia

cCo

mpa

ss®

Repo

rt a

nd A

T/AF

Sum

mar

y, re

gard

less

of E

CG S

tora

gepr

ogra

mm

ing

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

an

d fo

r dem

onst

ratio

n pu

rpos

es o

nly.

11

hO

ME

SYST

EMS

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RVIE

W

TRO

Ub L

ESh

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TIN

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S TO

RED

EPI

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ES

REVE

AL

L IN

Q™

ICM

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NA

L D

I Ag

NO

STIC

S

FOLL

OW

-UP

Prog

ram

min

g an

d Pr

int

a.M

ake

any

nece

ssar

y pr

ogra

mm

ing

chan

ges.

b. Pr

int “

Chan

ges T

his S

essio

n” a

nd fi

nal r

epor

ts. C

lick

on S

essio

n ic

on, t

hen

sele

ct“C

hang

es T

his S

essio

n”.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.

12

hO

ME

SYST

EMS

OVE

RVIE

W

TRO

Ub L

ESh

OO

TIN

g

S TO

RED

EPI

SOD

ES

REVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

FOLL

OW

-UP

To s

ave

data

Savi

ng to

Med

ia a

nd E

ndin

g Se

ssio

n

1.Se

lect

ic

on.

2.Se

lect

Sav

e To

Med

ia…

3. In

sert

med

ia in

to p

rogr

amm

er(U

SB o

r disk

ette

).

4.Pr

ess S

ave.

5. W

hen

com

plet

e, re

mov

ean

d la

bel m

edia

.

6. Se

lect

End

Ses

sion

.

7. Se

lect

End

Now

.

1.

2. 4.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.

13

hO

ME

SYST

EMS

OVE

RVIE

W

TRO

Ub L

ESh

OO

TIN

g

S TO

RED

EPI

SOD

ES

REVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

FOLL

OW

-UP

To re

trie

ve p

revi

ousl

y st

ored

dat

a

Relo

adin

g fro

m M

edia

1.Se

lect

icon

.

2.Se

lect

Oth

er.

3. Se

lect

Rev

eal L

INQ

– R

ead

From

Med

ia.

4.In

sert

med

ia.

5.Se

lect

Sta

rt.

6.Se

lect

Ope

n Fi

le …

7.Se

lect

file

and

pre

ss O

pen

File

.

1.

3.

2.

5.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for

dem

onst

ratio

n pu

rpos

es o

nly.

14

hO

ME

SYST

EMS

OVE

RVIE

W

TRO

Ub L

ESh

OO

TIN

g

S TO

RED

EPI

SOD

ES

REVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

FOLL

OW

-UP

R-W

ave

Ampl

itude

Und

erse

nsin

g

Trou

bles

hoot

ing

Stor

ed E

piso

des

The

follo

win

g is

an e

xam

ple

of R

-wav

e un

ders

ensin

g, w

hich

may

lead

to fa

lse d

etec

tions

of

brad

y or

pau

se e

piso

des.

Not

e th

at th

ere

is no

“VS”

und

er th

e R

wav

es in

the

red

box.

If di

stin

ct R

wav

es a

re n

ot m

arke

d as

VS:

• Con

sider

pro

gram

min

g th

e se

nsiti

vity

toa

mor

e se

nsiti

ve (l

ower

num

ber)

valu

e (fo

rex

ampl

e, fr

om 0

.035

to 0

.025

mV*

)

Util

ize th

e zo

om fu

nctio

n to

ana

lyze

stor

ed

ECG

s at a

ppro

pria

te sc

ale

and

ampl

itude

.

*Not

e: It

is im

port

ant t

o ch

eck

for P

-wav

e ov

erse

nsin

g w

hen

prog

ram

min

g th

e se

nsiti

vity

to a

mor

e se

nsiti

ve v

alue

.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.15

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

R EVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

R-W

ave

Ampl

itude

Ove

rsen

sing

The

follo

win

g is

an e

xam

ple

of R

-wav

e ov

erse

nsin

g, w

hich

may

lead

to fa

lse d

etec

tions

of

Tach

y ep

isode

s. N

ote

that

ther

e is

T-w

ave

over

sens

ing

iden

tifie

d by

the

red

arro

ws.

If di

stin

ct T

-wav

es o

r P-w

aves

are

mar

ked

as V

S, F

S, o

r TS:

• If T

-wav

es a

re m

arke

d as

VS,

FS,

or T

S,

cons

ider

pro

gram

min

g a

long

er d

ecay

de

lay

perio

d• I

f P w

aves

are

mar

ked

as V

S, F

S, o

r TS,

co

nsid

er p

rogr

amm

ing

the

sens

itivi

ty to

a

less

sens

itive

(hig

her n

umbe

r) va

lue

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.16

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

REVE

AL

LIN

Q™

ICM

A

DD

ITIO

NA

L D

IAg

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

To d

iscrim

inat

e ve

ry re

gula

r AT

rhyt

hms f

rom

ver

y re

gula

r sin

us rh

ythm

, sel

ecta

ble

low

er ra

te

cuto

ffs c

an b

e ad

ded

to th

e “D

etec

t Ver

y Re

gula

r AT

Rhyt

hms”

alg

orith

m.

Cons

ider

the

follo

win

g if

very

regu

lar s

inus

rh

ythm

s are

bei

ng d

etec

ted

as A

T:• I

ntrin

sic in

terv

als >

900

ms p

rogr

am“O

n-Ra

tes ≥

67

bpm

” (se

e ab

ove

ECG

strip

and

inte

rval

s exa

mpl

e)

• Int

rinsic

inte

rval

s < 9

00 m

s pro

gram

“On-

Rate

s ≥ 1

00 b

pm”

• Int

rinsic

inte

rval

s < 6

00 m

s pro

gram

“Off”

AT D

etec

tion

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.

17

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

R EVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

AF O

nly

Det

ectio

n

Prog

ram

min

g D

etec

tion

Para

met

ers

To p

rogr

am A

T/AF

det

ectio

n pa

ram

eter

s:1.

Sele

ct P

aram

eter

s2.

Sele

ct A

T/AF

Det

ectio

n

AT/A

F D

etec

tion

type

in A

F O

nly,

AF D

etec

tion

in B

alan

ced

Sens

itivi

ty, a

nd E

ctop

y Re

ject

ion

in

Nom

inal

sett

ing

will

wor

k be

st fo

r the

maj

ority

of p

atie

nts.

Med

troni

c re

com

men

ds th

ese

sett

ings

for o

ptim

al a

trial

fibr

illatio

n bu

rden

de

tect

ion.

*

If fa

lse p

ositi

ves a

re n

oted

in A

F O

nly

mod

e (fo

r exa

mpl

e: ir

regu

lar s

inus

rhyt

hm o

r sin

us

with

freq

uent

PAC

s), c

onsid

er re

prog

ram

min

g de

tect

ion

to a

less

sens

itive

val

ue, a

nd E

ctop

y Re

ject

ion

to “A

ggre

ssiv

e”. I

f it i

s des

ired

to in

crea

se se

nsiti

vity

to d

etec

ting

atria

l fib

rilla

tion,

co

nsid

er re

prog

ram

min

g de

tect

ion

to a

mor

e se

nsiti

ve v

alue

.

Onl

y if

it is

susp

ecte

d or

kno

wn

that

the

patie

nt h

as a

trial

tach

ycar

dia

or a

trial

flut

ter d

oes

Med

troni

c re

com

men

d pr

ogra

mm

ing

AT/A

F D

etec

tion

type

to A

T fo

r a sh

ort d

urat

ion

of ti

me,

an

d af

ter d

iagn

osis

of A

T re

prog

ram

bac

k to

AF

Onl

y m

ode.

* Bu

rden

is d

efin

ed a

s the

cum

ulat

ive

time

in A

T/AF

. Tim

e in

AT/

AF (Q

uick

Loo

k™ s

cree

n, C

ardi

ac C

ompa

ss®,

and

AT/A

F Su

mm

ary)

will

repo

rt to

tal t

ime

of A

F ep

isode

s whe

n pr

ogra

mm

ed to

AF

Onl

y. W

hen

prog

ram

med

toAT

/AF

time

in A

T/AF

is re

port

ed a

s the

com

bine

d to

tal t

ime

of A

T an

d AF

epi

sode

s.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.18

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

R EVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

AF F

alse

Pos

itive

Det

ectio

n

Due

to e

ctop

y rh

ythm

s (i.e

., sin

us a

rrhyt

hmia

, PAC

s, PV

Cs, b

igem

iny,

trige

min

y)

If fa

lse

posi

tive

dete

ctio

ns d

ue to

ect

opy

rhyt

hms:

Cons

ider

one

, tw

o, o

r al

l thr

ee o

ptio

ns b

elow

:

1. If

Ecto

py R

ejec

tion

iscu

rrent

ly O

ff –

cons

ider

prog

ram

min

g to

“Nom

inal

”; If

Ecto

pyRe

ject

ion

is cu

rrent

lyN

omin

al –

con

sider

prog

ram

min

g to

“Agg

ress

ive”

.

2. Pr

ogra

m A

T/AF

ECG

Reco

rdin

g Th

resh

old

to a

long

er E

CG.

3. Co

nsid

er p

rogr

amm

ing

AF D

etec

tion

to “L

ess”

or “L

east

” Sen

sitiv

e.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.19

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

R EVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

If af

ter r

evie

win

g st

ored

and

real

-tim

e st

rips,

it is

nec

essa

ry to

repr

ogra

m

sens

ing,

do

the

follo

win

g:

Opt

imiz

ing

Sens

ing

Para

met

ers

Sum

mar

y

1. En

ter t

he P

aram

eter

s scr

een

byto

uchi

ng th

e

icon

.

2.Se

lect

Sen

sing

… u

nder

Add

ition

al S

ettin

gs.

3.Ad

just

as n

eede

d:

• If d

istin

ct R

wav

es a

re n

ot m

arke

d as

VS:

– Pr

ogra

m se

nsiti

vity

to a

low

er se

ttin

g(fo

r exa

mpl

e, fr

om 0

.035

to 0

.025

mV*

)

• If P

wav

es a

re m

arke

d as

VS,

pro

gram

sens

itivi

ty to

a h

ighe

r set

ting

• If T

wav

es a

re m

arke

d as

VS,

pro

gram

a lo

nger

dec

ay d

elay

per

iod

4.Pr

ess O

K.

5.Pr

ess P

ROg

RAM

.6.

Verif

y ch

ange

s are

app

ropr

iate

.

* Med

troni

c re

com

men

ds p

rogr

amm

ing

the

sens

itivi

ty to

a

sett

ing

sligh

tly a

bove

the

P-w

ave

ampl

itude

.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.20

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

R EVE

AL

L IN

Q™

ICM

A

DD

ITIO

NA

L D

I Ag

NO

STIC

S

TRO

UbL

ESH

OO

TIn

g

STO

REd

EPI

SOd

ES

Card

iac

Com

pass

® Re

port

Card

iac

Com

pass

Rep

ort p

rovi

des

trend

ing

data

, whi

ch in

clud

es d

aily

AT/

AF

burd

en, V

. rat

e du

ring

AT/A

F, av

erag

e da

y an

d ni

ght V

. rat

e, d

aily

act

ivity

, and

hea

rt

rate

var

iabi

lity.

Not

e:

Card

iac

Com

pass

Rep

ort i

s ava

ilabl

e in

a

prin

ted

form

at a

nd o

n th

e Ca

reLi

nk®

web

site.

1. Se

lect

i

con.

2. S

elec

t Ava

ilabl

e Re

port

s …

3.Ch

eck

desir

ed re

port

s.

4.Se

lect

Prin

t Now

. All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.21

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

TRO

UbL

ESh

OO

TIN

g

S TO

RED

EPI

SOD

ES

REVE

aL

LIn

Q™

ICM

a

dd

I TIO

na

L d

Iag

nO

STIC

S

Rate

his

togr

am

The

Rate

Hist

ogra

m re

port

is

base

d on

a c

ontin

uous

re

cord

ing

of v

entri

cula

r rat

es

since

the

last

pat

ient

sess

ion.

Th

e Ra

te H

istog

ram

s rep

ort

pres

ents

hea

rt ra

te d

ata

in

2 ty

pes o

f hist

ogra

ms:

• v

entri

cula

r rat

e an

d ve

ntric

ular

• r

ate

durin

g AT

/AF.

The

repo

rt in

clud

es d

ata

from

the

curre

nt (s

ince

last

sess

ion)

col

lect

ion

perio

d.

Not

e:

Avai

labl

e as

a p

rinte

d re

port

and

on

the

Care

Link

® Net

wor

k.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.22

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

TRO

UbL

ESh

OO

TIN

g

STO

RED

EPI

SOD

ES

REVE

aL

LIn

Q™

ICM

a

dd

ITIO

na

L d

Iag

nO

STIC

S

AT/A

F Su

mm

ary

AT/A

F Su

mm

ary

repo

rt

give

s an

over

view

of a

ll at

rial a

rrhyt

hmia

s det

ecte

d,

incl

udin

g pe

rcen

tage

of t

ime

in A

T/AF

, ave

rage

tim

e in

AT

/AF

per d

ay, a

nd n

umbe

r of

episo

des a

t a g

iven

dur

atio

n.

not

e: A

vaila

ble

as a

prin

ted

repo

rt. N

ot a

vaila

ble

on th

e Ca

reLi

nk® N

etw

ork.

All p

atie

nt a

nd c

linic

al d

ata

are

fictit

ious

and

for d

emon

stra

tion

purp

oses

onl

y.23

hO

ME

SYST

EMS

OVE

RVIE

W

FOLL

OW

-UP

TRO

UbL

ESh

OO

TIN

g

STO

RED

EPI

SOD

ES

REVE

aL

LIn

Q™

ICM

a

dd

ITIO

na

L d

Iag

nO

STIC

S

MED

TRO

NIC

CO

NFI

DEN

TIAL

– F

OR

INTE

RNAL

USE

ON

LY

brie

f Sta

tem

ent

Reve

al L

InQ

™ L

nQ

11 In

sert

able

Car

diac

Mon

itor a

nd

Patie

nt a

ssis

tant

Indi

catio

ns: R

evea

l LIn

Q L

nQ

11 In

sert

able

Car

diac

M

onito

r Th

e Re

veal

LIN

Q In

sert

able

Car

diac

Mon

itor i

s an

impl

anta

ble

patie

nt-a

ctiv

ated

and

aut

omat

ical

ly-a

ctiv

ated

mon

itorin

g sy

stem

that

reco

rds s

ubcu

tane

ous E

CG a

nd is

indi

cate

d in

the

follo

win

g ca

ses:

• pat

ient

s with

clin

ical

synd

rom

es o

r situ

atio

ns a

t inc

reas

ed ri

skof

car

diac

arrh

ythm

ias

• pat

ient

s who

exp

erie

nce

trans

ient

sym

ptom

s suc

h as

dizz

ines

s, pa

lpita

tion,

sync

ope,

and

che

st p

ain,

that

may

sugg

est a

car

diac

arrh

ythm

ia

Patie

nt a

ssis

tant

: The

Pat

ient

Ass

istan

t is i

nten

ded

for

unsu

perv

ised

patie

nt u

se a

way

from

a h

ospi

tal o

r clin

ic. T

hePa

tient

Ass

istan

t act

ivat

es th

e da

ta m

anag

emen

t fea

ture

in th

eRe

veal

Inse

rtab

le C

ardi

ac M

onito

r to

initi

ate

reco

rdin

g of

car

diac

even

t dat

a in

the

impl

ante

d de

vice

mem

ory.

Cont

rain

dica

tions

: The

re a

re n

o kn

own

cont

rain

dica

tions

for t

he im

plan

t of t

he R

evea

l LIN

Q In

sert

able

Car

diac

Mon

itor.

How

ever

, the

pat

ient

’s pa

rtic

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med

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con

ditio

n m

aydi

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e w

heth

er o

r not

a su

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aneo

us, c

hron

ical

ly im

plan

ted

devi

ce c

an b

e to

lera

ted.

War

ning

s/Pr

ecau

tions

: Rev

eal L

InQ

Ln

Q11

Inse

rtab

le

Card

iac

Mon

itor

Patie

nts w

ith th

e Re

veal

LIN

Q In

sert

able

Car

diac

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itor

shou

ld a

void

sour

ces o

f dia

ther

my,

high

sour

ces o

f rad

iatio

n,

elec

trosu

rgic

al c

aute

ry, e

xter

nal d

efib

rilla

tion,

lith

otrip

sy,

ther

apeu

tic u

ltras

ound

and

radi

ofre

quen

cy a

blat

ion

to a

void

el

ectri

cal r

eset

of t

he d

evic

e, a

nd/o

r ina

ppro

pria

te se

nsin

g as

des

crib

ed in

the

Med

ical

pro

cedu

re a

nd E

MI p

reca

utio

ns

man

ual. M

RI sc

ans s

houl

d be

per

form

ed o

nly

in a

spec

ified

MR

envi

ronm

ent u

nder

spec

ified

con

ditio

ns a

s des

crib

ed in

the

Reve

al L

INQ

MRI

Tec

hnic

al M

anua

l.

Patie

nt a

ssis

tant

: Ope

ratio

n of

the

Patie

nt A

ssist

ant n

ear

sour

ces o

f ele

ctro

mag

netic

inte

rfere

nce,

such

as c

ellu

lar

phon

es, c

ompu

ter m

onito

rs, e

tc., m

ay a

dver

sely

affe

ct th

e pe

rform

ance

of t

his d

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e.

Pote

ntia

l Com

plic

atio

ns: P

oten

tial c

ompl

icat

ions

incl

ude,

bu

t are

not

lim

ited

to, d

evic

e re

ject

ion

phen

omen

a (in

clud

ing

loca

l tiss

ue re

actio

n), d

evic

e m

igra

tion,

infe

ctio

n, a

nd e

rosio

n th

roug

h th

e sk

in.

See t

he d

evice

man

ual f

or d

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led

info

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ion

rega

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g th

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t pro

cedu

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tions

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s, pr

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tions

, and

pot

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l com

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atio

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cons

ult M

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nic’s

web

site a

t ww

w.m

edtro

nic.

com

.

Caut

ion:

Fed

eral

law

(USA

) res

trict

s thi

s dev

ice

to sa

le b

y or

on

the

orde

r of a

phy

sicia

n.

24

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inte

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Prog

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atio

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app

ropr

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par

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ed o

n th

e pa

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nditi

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acin

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stem

use

d. T

he M

edtro

nic

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Link

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used

onl

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r pro

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plan

tabl

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Med

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Vita

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See

the

devi

ce m

anua

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inst

ruct

ions

for u

se, in

dica

tions

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tions

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s, pr

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tions

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entia

l adv

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eve

nts.

For f

urth

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leas

e ca

ll Med

troni

c at

1 (8

00) 3

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and/

or co

nsul

t M

edtro

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web

site

at w

ww

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m.

Caut

ion:

Fed

eral

law

(USA

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tric

ts th

is de

vice

to s

ale

by o

r on

the

orde

r of a

phy

sicia

n.

ww

w.m

edtr

onic

.com

ww

w.m

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onic

.com

Med

tron

ic, I

nc.

710

Med

tron

ic P

arkw

ay

Min

neap

olis,

MN

554

32-5

604

USA

Te

l: (7

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000

Fax:

(76

3) 5

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879

Med

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SA, I

nc.

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free:

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00) 3

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Tel:

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3 24

1004

UC201401404a EN © Medtronic, Inc. 2015. Minneapolis, MN. All Rights Reserved. 05/2015

25

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